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Diseases of the Brain, 
Head and Neck, 

Spine 




Diagnosticimaging 

and Interventional Techniques 



Editors 

G.K.von Schulthess 
Ch.L Zollikofer 





Springer 



Diseases ofliie Brain, Head and Neck, Spine 

Diagnostic Imaging and Interventional Teehniques 




Springer-Verlag Italia Sri. 




G.K. von Schulthess • Ch.L. Zollikofer (Eds) 



DISEASES OF THE 
BRAIN, HEAD AND 
NECK, SPINE 

DIAGNOSTIC IMAGING AND INTERVENTIONAL 
TECHNIQUES 



36th International Diagnostic Course 
in Davos (IDKD) 

Davos, March 2 7 -April 2, 2004 

presented by the Foundation for the 

Advancement of Education in Medical Radiology, Zurich 




Springer 




G. K. von Schulthess 
Universita tsspital 
Nuklearmedizin 
8091 Zii rich, Switzerland 



Ch. L. Zollikofer 
Kantonsspital 
Institut fiir Radiologic 
8401 Winterthur, Switzerland 



© Springer- Verlag Italia 2004 

Originally published by Springer-Verlag Italia, Milano in 2004 
springeronlinexom 

ISBN 978-8^700251-7 ISBN 978-88-470^2131-0 (eBoook) 

DOl 10.1007/978-88-470-2131-0 

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IDKD 2004 



Preface 



The International Diagnostic Course in Davos (IDKD) offers a unique learning 
experience for imaging specialists in training as well as for experienced radi- 
ologists and clinicians wishing to be updated on the current state of the art and 
the latest developments in the fields of imaging and image-guided interventions. 

This annual course is focused on organ systems and diseases rather than on 
modalities. This year’s program deals with neuroradiology and radiology of the 
spine. During the course, the topics are discussed in group seminars and in ple- 
nary sessions with lectures by world-renowned experts and teachers. While the 
seminars present state-of-the-art summaries, the lectures are oriented towards fu- 
ture developments. 

These proceedings represent a condensed version of the contents presented un- 
der the 20 topics dealing with imaging and interventional therapies in the neuro- 
radiology and radiology of the spine. The topics encompass all the relevant imag- 
ing modalities including conventional x-rays, computed tomography, nuclear 
medicine, ultrasound and magnetic resonance angiography, as well as image-guid- 
ed interventional techniques. 

The volume is designed to be an ""aide-memoire” for the course participants so 
that they can fully concentrate on the lectures and participate in the discussions 
without the need of taking notes. Additional information is found on the web page 
of the IDKD fhttp//: www.idkd.ch ~). 



G.K. von Schulthess 
Ch.L. Zollikofer 




IDKD 2004 



Table of Contents 



Brain Tumors 

E.A. Knopp, W. Montanera 3 

Neuroimaging of Cerebral Vessel: Evidence-based Medicine 
in the Evaluation of Acute Stroke and Aneurysm Detection 

M. E. Jensen 11 

Evaluation of the Cerebral Vessels 

R. Willinsky 14 

Imaging and Management of Acute Stroke 

W.T.C. Yuh, T. Taoka, T. Ueda, M. Maeda 20 

Brain Ischemia 

R. von Kummer 27 

Haemorrhagic Cerebral Vascular Disease 

J. Byrne 34 

Hemorrhagic Vascular Phatology 

M. Forsting, I. Wanke 36 

Demyelinating Diseases 

K. K. Koeller, R.G. Ramsey 44 

Brain Degeneration and Aging 

M.A. van Buchem 50 

Imaging the Effects of Systemic Metabolic Diseases on the Brain 

M. Castillo 55 

Neuroradiological Diagnosis of Craniocerebral and Spinal Trauma: 

Current Concepts 

RM. Parizel, C.D. Phillips 60 

Nontraumatic Neuroemergencies 

J.R. Hesselink, S. Atlas 73 

Imaging the Patient with Seizures 

P. Ruggieri, A. Nusbaum 77 

Infectious Diseases of the Central Nervous System 

V Dousset 85 




VIII 



Cerebral Infections 

D. Mikulis 93 

Diseases of the Sella 

J.F. Bonneville, W. Kucharczyk 100 

Neuroimaging Diagnosis of Primary Brain Neoplasms in Childhood 

W.S. Ball 107 

Central Nervous System Diseases in Children 

C. Raybaud 112 

Orbit and Visual Pathways 

M.F. Mafee, D.M. Yousem 118 

Temporal Bone and Auditory Pathways 

J.W. Casselman 124 

Imaging the Temporal Bone 

F. Veillon, S. Riehm 130 

Imaging the Pharynx and Oral Cavity 

B. Schuknecht, A.N. Hasso 136 

Imaging of the Larynx 

H.D. Curtin 146 

Imaging the Larynx and Hypopharynx 

M. Becker 149 

Paranasal Sinuses and Nose: Normal Anatomy and 
Pathologic Processes 

L. A. Loevner 158 

Nose, Paranasal Sinuses and Adjacent Spaces 

R. Maroldi, D. Farina, R Nicolai 165 

Degenerative Diseases of the Spine 

B. C. Bowen 174 

Degenerative Diseases and Pain Syndromes 

J.L. Drape 181 

Neoplastic Spinal Cord Disease 

D. L. Baleriaux 184 

Spinal Trauma and Spinal Cord Injury 

A.E. Flanders 189 

Spinal Inflammation and Demyelinating Diseases 

C. Manelfe 193 

Spinal Inflammation and Demyelinating Diseases 

M. Leonard!, M. Maffei 197 




SEMINARS 




IDKD 2004 



Brain Tumors 

E.A. Knopp^, W. Montanera^ 

^ Section of Neuroradiology, Department of Radiology and Neurosurgery, NYU School of Medicine, New York, NY, USA 
^Department of Medical Imaging, St. Michael’s Hospital, University of Toronto, Toronto, Canada 



Introduction 

The designation “brain tumor” is commonly applied to a 
wide variety of intracranial mass lesions, each distinct in 
location, biology, treatment, and prognosis. Since many 
of these lesions do not arise from brain parenchyma, the 
more appropriate term is “intracranial tumor”. Since the 
category encompasses both neoplasms and non-neoplas- 
tic mass lesions, the word “tumor” is used in its broadest 
sense to indicate a space-occupying mass. 

Epidemiological data indicate that the annual inci- 
dence of intracranial tumors is 11-19 per 100000 per- 
sons. Metastases to the brain from a systemic primary 
cancer outside the central nervous system are even 
more common. Intracranial tumors can cause focal or 
generalized neurological symptoms. Headache, nausea, 
vomiting and occasional cranial nerve palsy (especial- 
ly involving the sixth cranial nerve) may result from in- 
creased intracranial pressure. Focal symptoms and 
signs (e.g. paresis, visual deficit, aphasia) usually re- 
flect the intracranial location of the tumor and the af- 
fected area of the brain. The frequency and duration of 
symptoms and signs also vary with the type of tumor. 
Rapidly growing tumors may exhibit symptoms earlier, 
with less overall tumor bulk than a more slowly grow- 
ing tumor. 

Headache occurs in about half of patients with brain 
tumors and is typically worse in the morning and im- 
proves after erect posture. Seizures are common (in 15%- 
95% of cases) and may be focal or generalized. Focal 
symptoms like hemiparesis and dysphasia are usually 
subacute in onset and progressive. 

The only unequivocal risk factor for intracranial tu- 
mors, past cranial radiation, has been linked to both 
glial and meningeal neoplasms. Primary central ner- 
vous system lymphoma has tripled in incidence over 
the past two decades, largely due to the increased inci- 
dence in patients with acquired immunodeficiency syn- 
drome. However, the incidence of lymphoma has also 
risen in the immunocompetent population with no 
known environmental exposure or behavioral risk fac- 
tor [1-9]. 



Imaging Features of Intracranial Tumors 

Prognosis and treatment of intracranial tumors are high- 
ly dependent on tumor histology. Predicting histology 
from preoperative imaging procedures depends largely 
on establishing the correct location of the origin of the 
mass. Specifically, the radiologist must first establish if 
the mass arises from within the brain parenchyma (in- 
tra-axial) or arises outside the brain parenchyma (extra- 
axial), whereby symptoms are usually due to brain com- 
pression. Radiologically identifiable anatomical clues 
that a tumor is extra-axial in location include the fol- 
lowing: 

(a) Widening of the ipsilateral subarachnoid space 

(b) Cerebrospinal fluid (CSF) cleft between mass and 
brain parenchyma 

(c) Deviation of pial vessels between mass and brain 
tissue 

(d) Buckling of white matter 

(e) Bony changes (e.g. hyperostosis in meningioma) 

Once established as intra-axial or extra-axial, the spe- 
cific location of the mass becomes equally important in 
imaging analysis since certain histological types of in- 
tracranial tumor tend to occur with higher frequency in 
specific locations. Thus, accurate compartmentalization 
of the mass limits the differential diagnosis to a relevant 
few tumors (Table 1) and helps direct further imaging 
evaluation and treatment [1-5]. 

Beyond the location of the mass, it is important to note 
other features in the imaging analysis of intracranial tu- 
mors further increase the likelihood of arriving at an ac- 
curate diagnosis and evaluating accurately the effect of 
the mass on adjacent brain tissue. Histologic features 
such as calcium or fat can be easily seen on cross-sec- 
tional imaging. The density of the mass on computed to- 
mography (CT) and the signal intensity on T2-weighted 
magnetic resonance images can offer clues to cell com- 
position and relative water content (e.g. nucleus-cyto- 
plasm ratio). Compressive effects on adjacent brain tis- 
sue, extent of vasogenic edema accompanying the mass, 
and complicating hydrocephalus are easily and noninva- 
sively assessed. Certain tumors have a higher likelihood 




4 



E.A. Knopp, W. Montanera 



Table 1. Regional classification of common intracranial tumors 



Intraventricular 


Cavernous sinus 


Ependymoma 


Meningioma 


Subependymoma 


Schwannoma 


Choroid plexus papilloma 


Pituitary adenoma 


Central neurocytoma 


Metastasis 


Colloid cyst 


Cerebellopontine angle 


Giant cell astrocytoma 


Schwannoma 


Pineal region 


Meningioma 


Pineocytoma 


Epidermoid 


Germ cell tumor 


Arachnoid cyst 


Primitive neuroectodermal 


Paraganglioma 


tumor (PNET) 


Metastasis 


Tectal glioma 


Skull base 


Meningioma 


Chordoma 


Dermoid 


Chondrosarcoma 


Arachnoid cyst 


Paraganglioma 


Sella and suprasellar region 


Metastasis and myeloma 


Pituitary adenoma 


Sinonasal carcinoma 


Craniopharyngioma 


Esthesioneuroblasoma 


Meningioma 


Lymphoma and leukemia 


Rathke’s cyst 


Foramen magnum 


Chiasmatic glioma 


Meningioma 


Dermoid and epidermoid 


Schwannoma 


Germ cell tumor 


Brainstem glioma 
Ependymoma 



of presenting with hemorrhage that can be readily diag- 
nosed on CT or magnetic resonance imaging (MRI). 
Furthermore, these conventional imaging tools can be 
used to predict vascularity of intracranial tumors that 
have not presented with hemorrhage. Intravenous con- 
trast agents add further to the conventional imaging 
analysis of intracranial tumors by increasing conspicuity 
and demonstrating enhancement characteristics that help 
increase specificity. 

Advanced Imaging Techniques in Intracranial 
Tumors 

With the advent of faster imaging techniques, MRI can 
now depict various aspects of brain function in addition 
to brain anatomy. 

Brain Diffusion 

Diffusion imaging uses echo planar sequences. What is 
being imaged is the macromolecular motion of water 
within the extracellular space. In the normal brain this 
space is defined by the boundaries of axonal pathways. 
The axon bundles restrict the patterns of motion of water. 
This restriction occurs in a variety of directions in normal 
brain. In abnormal brain, these patterns are perturbed. 
Diffusion imaging relies on these perturbations. The most 
significant limitation is due to motion. Since what is be- 
ing imaged in the first place is motion, the sequences 



have to be inherently motion sensitive. The echo planar 
methods do limit the amount of extrinsic motion but they 
do not completely eliminate it. 

The principle application for diffusion imaging is in 
the identification of hyperacute infarct. This determina- 
tion can be made well in advance of T2 changes (minutes 
rather than hours). We use infarct as an example to ex- 
plain the principles involved. With the onset of ischemia, 
there is breakdown of cell membrane Na-K ATPase 
pumps. This results in an influx of sodium ions into the 
cell. Water then follows, resulting in cell swelling. All 
this occurs within minutes of cessation of blood flow. At 
this time, the cells are still viable, however the extracel- 
lular space is compressed secondary to the swollen cells. 
The water in this compressed extracellular space is re- 
stricted in its ability to move. It is this restriction that the 
diffusion sequence detects. One can therefore see how 
diffusion imaging can detect hyperacute infarct. 

The major problem with the interpretation of these im- 
ages lies in the anisotropic patterns of motion; one there- 
fore has to image in 3 orthogonal planes in order to 
achieve anisotropy. Once this is achieved, the method is 
inherently reproducible and easy to interpret. 

A second application of diffusion techniques is in the 
differentiation of edema (vasogenic) from gliotic change. 
This has implication in tumor imaging and subsequent 
follow-up. Although infiltrative brain parenchyma has a 
diffusion abnormality, it does not give as significant a 
signal change on a diffusion-weighted image as does va- 
sogenic edema. By using more advanced diffusion tech- 
niques, diffusion-tensor imaging and tractography, one 
can see more subtle infiltrative changes based upon the 
distortions in normal brain anisotropy. As glial neoplasms 
infiltrate along axonal pathways, they cause an inherent 
change in the fractional anisotropy along with visible 
changes seen on tractography. 

Diffusion techniques readily enable one to differenti- 
ate solid from true cystic lesions. This in certain instances 
can aid in preoperative surgical planning [10-13]. 

Brain Perfusion 

Perfusion imaging of the brain is a means to define the 
cerebral (capillary) blood volume by imaging during a 
bolus of contrast medium. This is different from conven- 
tional spin echo (SE) post-contrast imaging. In SE imag- 
ing, one is looking at the breakdown of the blood-brain 
barrier (in a similar fashion to CT). With perfusion imag- 
ing, the imaging is carried out during the first pass of 
contrast medium through the capillary bed. The imaging 
is finished before a significant amount of contrast medi- 
um crosses a disturbed blood-brain barrier. 

The echo planar sequences routinely employed rely on 
the susceptibility changes in the image due to the pres- 
ence of gadolinium. These changes manifest as a signal 
intensity drop. The drop is proportional to the “volume” 
of capillaries present. This method can be used in two 
major areas of imaging. 




Brain Tumors 



5 



The first one we discuss is in tumor imaging. In this 
instance, perfusion “maps” enable one to determine the 
volume of the capillaries in the lesion in question as well 
as in normal brain. This is useful in the differentiation of 
areas of higher-grade disease within neoplasms. This has 
implications in choosing biopsy sites. Tumor boundaries 
may also be better characterized. Perfusion methods also 
allow one to differentiate therapeutic necrosis (secondary 
to radiation as well as high-dose chemotherapy). In these 
instances, the contrast-enhancing mass, while not having 
an intact blood-brain barrier, does not have any increase 
in capillary volume: in fact this is significantly reduced 
(if not absent). This fact manifests as a “cold” region with 
perfusion techniques. 

The second (and more widely used) application is in 
the determination of hyperacute infarct. This is men- 
tioned here only for the sake of completeness. With in- 
farct, there is diminution of blood flow and an overall de- 
crease in the affected capillary blood volume. These 
changes occur prior to any significant T2 abnormality. In 
this regard, the perfusion map shows the infarct as a “cold 
spot”. 

There are, however, limitations in perfusion scanning. 
The primary limitation reflects the need to administer 
gadolinium. In order to achieve a high intravascular lev- 
el of gadolinium in a short, finite period of time, the con- 
trast medium must be administered in a rapid bolus and 
flush fashion. Standard rates of administration are on the 
order of 5 ml/s. This rate is difficult to standardize with 
a hand injection. The use of a power injector does sim- 
plify this, but instead adds significantly to the cost. A 
large-bore intravenous needle (20 gauge) is needed. The 
second major limitation has to due with the necessity to 
post-process the data. Perfusion maps based upon statis- 
tical significance need to be calculated. 

Previous work suggests that within a given tumor var- 
ious grades of malignancy can co-exist. It has also been 
shown that tumor grade is related to the integrity of the 
blood-brain barrier and to the density and character of the 
tumor neovascularity. Although the integrity of the blood- 
brain barrier has been studied with both CT and MRI, 
this characteristic alone has not been sufficient to predict 
tumor grade. With the advent of MRI methods that mea- 
sure relative cerebral blood flow (perfusion), it should be 
possible to explore the degree of neovascularity. Aronen 
et al. [14] used MRI perfusion techniques to obtain a 
cerebral blood volume map of gliomas and demonstrated 
that there is a correlation between the degree of perfusion 
(maximal cerebral blood volume) and the tumor mitotic 
activity and vascularity. In their study, however, one sam- 
ple was randomly obtained from each tumor via either 
biopsy or resection, and they were unable to directly cor- 
relate tumor pathology with the radiographic features. In 
contrast, our methodology of stereotactic serial biopsy 
assures precise sampling of the lesion and allows for tar- 
geting based upon imaging features [12, 14-18]. 



Clinical MR Spectroscopy 

Proton spectroscopy extends the diagnostic utility of the 
MRI brain examination beyond the typical structural im- 
ages of anatomy and provides another functional dimen- 
sion based on biochemical information. In a noninvasive 
manner, MRS provides valuable functional information 
that adds diagnostic value to the traditional MRI exam. 
The functional nature of the spectroscopy examination 
augments other functional MRI techniques such as diffu- 
sion, perfusion and blood oxygen level-dependent 
(BOLD) MRI studies. Together, these new diagnostic 
techniques are expanding the role of diagnostic MRI in 
the brain. 

The major biochemical compounds detected using 
proton MRS in normal and pathological brain as summa- 
rized in Table 2 and as follows: 

- A-Acetylaspartate (NAA) is a marker of neuronal via- 
bility and density. It is synthesized in neurons and 
transported along axons. NAA gives the highest meta- 
bolic peak on proton MRS with a frequency shift of 
2.0 ppm. NAA concentration increases in Canavan’s 
disease and decreases in physiologic conditions of 
birth (low concentration) and aging, neoplasia, hypox- 
ia, ischemia, infarct, epilepsy, infection, inflammation 
and neurodegenerative states. 

- Creatine (Cr) is generally used as an internal standard 
(reference) because its signal amplitude remains con- 
stant in most situations. Creatine, creatine kinase and 
phosphocreatine are central to the ADP/ATP energy 
pathway. The Cr peak, assigned at 3.03 ppm, is the sec- 
ond highest in proton MRS. Creatine concentration in- 
creases in trauma and aging, while it decreases with 
metastases. 

- Choline (Cho) is involved in synthesis of phospho- 
lipids and thus it is a membrane compound and indi- 
cator of cellular turnover. Cho gives the third highest 
peak on proton MRS, assigned at 3.2 ppm. Choline 
concentration increases in a wide variety of condi- 
tions: physiologic, recovery from insult, gliosis, neo- 
plasia, demyelination, inflammation and infection. It 
decreases in dementia, stroke and asymptomatic liver 
disease. 

- Glutamine (Gin) and glutamate (Glu) are astrocyte 
markers. Glutamate is an excitatory neurotransmitter, 
which in excess concentration is a neurotoxin. 
Disruption of Gln/Glu regulatory mechanisms has 
been implicated in the initiation of a cascade leading 
to neuronal damage and death. These amino acids are 
increased in ischemia, recovery from ischemia, and 
liver disease. They are decreased primarily in 
Alzheimer’s disease. 

- Lactate (Lac) is seen in processes with cellular necro- 
sis; normally it is not found in brain. Lactate is ob- 
served in pathologic processes with increased anaero- 
bic metabolism. In proton MRS, lactate appears as a 
doublet configuration, with a peak assigned at 1.32 
ppm. 




6 E.A. Knopp, W. Montanera 



Table 2. Common biochemical compounds in brain detected by proton magnetic resonance spectroscopy (MRS) and their significance to 
brain imaging 



Compound 


Resonating structure 


Clinical significance 


A-Acetylaspartate (NAA) 


-CH3 moiety of NAA 


Marker for active neuronal tissue 


Lactate (Lac) 


-CH3 moiety of lactate 


Marker for low tissue oxygen and anaerobic 
glycolysis 


Creatine (Cr) 


-CH2 and -CH3 moieties of creatine and 
creatine phosphate 


Important bioenergetic compounds in all living 
cells 


Choline (Cho) 


-N^(CH3)3 moiety of all choline compounds, 
including choline, acetylcholine, 
phosphatidyl choline and others 


Important cell membrane components 


Lipid 

Myoinositol (MI) 

Glutamine (Glu), glutamate (Gin) 
Glucose (Glc) 


-CH2 and -CH3 moieties of adipose tissue 
storage fats (triglycerides) 

-CH moieties of inositol isomers 
-CH2 moieties of glutamate and glutamine 
-CH moieties of glucose 


The fatty acyl groups in phospholipid membrane 
bilayer appear as broad components in the 
baseline 



- Lipids are elevated in brain in pathologie processes 
such as infection, inflammation, tumor necrosis and 
stroke. Lipids within brain are associated with myelin, 
sphingomyelins, phospholipids, and lecithins. Be 
aware that extracerebral lipids can contaminate vol- 
umes of interest (VOI). 

- Myoinositol is almost exclusively found in astrocytes. 
Its major role is as an osmolyte. Chemically it looks 
like glucose, having a variable amplitude, assigned to 
3.56 ppm. Its concentration is increased in patients 
with Alzheimer’s disease, in neonates (compared to 
adults), and in hyperosmolar states. It is decreased in 
hepatic encephalopathy and hyponatremia. 

The basic patterns observed in MRS are as follows: 

- CSF. Cerebral metabolites are virtually absent from 
CSF. Lactate and glucose are present in normal CSF; 
if included in VOI, they reduce the signal to noise ra- 
tio (SNR) of cerebral metabolites. 

- Hypoxic-ischemic cascade: loss of NAA; appearance 
of lactate; increased glutamine and glutamate; excess 
lipid is frequently found; and ultimately loss of crea- 
tine. 

- Abscess: metabolites not usually detected but acetate 
peak is at 1.92 ppm; leucine, isoleucine, valine, succi- 
nate, pyruvate and lactate and lipids can be found. 

- HIV toxoplasmosis: increased lactate and lipids at 1.3 
and 0.9 ppm, respectively; decreased myoinositol, 
NAA, Cr, Cho. The diagnostic accuracy is approxi- 
mately 100%. 

- HIV CNS lymphoma: increased choline, lactate and 
lipids; decreased myoinositol, NAA and Cr. The diag- 
nostic accuracy is 75%. 

- PML: increased myoinositol and Cho; decreased Cr 
and NAA; lower levels of lactate and lipids. The diag- 
nostic accuracy is 83%. 

- Cerebral neoplasms, generally: low or absent NAA; 
low Cr; elevated Cho and lipid; lactate levels are vari- 
able. 



Neuropathological applications of proton MRS in- 
clude histological grading of tumors based on the Cho/Cr 
ratio [19]: 

- Low grade hamartomas, <1.5 

- Intermediate gliomas, 1. 5-2.0 

- High-grade gliomas, >2.0 

The Cho/NAA ratio can be used in the differential di- 
agnosis of intracranial tumors [20]: 

- Normal, 0.75 

- Low-grade glioma, 1.86 

- Ependymoma, 1.8 

- PNET, 7.5 

- Choroid plexus carcinoma, 8.4 

- High-grade glioma, 16.6 

In radiation necrosis, the proton MRS profile is low in 
all metabolites, especially lactate and lipids (in contrast 
to recurrent tumor); however choline is increased. These 
observations correlate with those on positron emission 
tomography (PET). 

Finally, proton MRS can be used to distinguish prima- 
ry and secondary neoplasms. In primary glial tumors, the 
peritumoral MRS spectra demonstrate elevated choline. 
In secondary tumors or metastases, choline is not elevat- 
ed in peritumoral tissue. This correlates with MR perfu- 
sion findings in which there is increased relative cerebral 
blood volume (rCBV) in the peritumoral region of pri- 
mary neoplasms but not of secondary tumors. The basis 
for this difference is the presence of infiltrative tumor 
cells in the first instance and the presence of edema in the 
second case [10, 18, 21]. 

Technical Aspects of Proton MRS 

The single voxel technique (one-dimensional single vox- 
el spectroscopy, SVS) permits interrogation of brain 
metabolites in a single location selected by the operator. 
Typical imaging time is 2-8 min, depending on voxel di- 
mensions. SVS pulse sequences include stimulated echo 




Brain Tumors 



7 



acquisition mode (STEAM) and point-resolved spec- 
troscopy (PRESS). 

- STEAM can be performed as 90°-90°-90°-echo, as 
well as gradient echo with low signal-to-noise ratio 
(SNR). Advantages are the short echo time (TE) that 
allows detection of metabolites with short T2 relax- 
ation times (e.g. glutamine, glutamate, myoinositol, 
lipids), and more effective water suppression. 
Disadvantages are lower SNR and extreme sensitive 
to motion. 

- PRESS is performed as 90”-180°-180°-echo, as well as 
spin echo with high SNR. Advantages are higher SNR. 
Disadvantages are long TE (135 ms), longer acquisi- 
tion times and the possibility to “miss” metabolites 
with short TE. 

Chemical shift imaging (CSI) extends the spectroscop- 
ic technique to multivoxel arrays covering a large vol- 
umes of interest in a single measurement. This two-di- 
mensional technique permits the localization of chemical 
changes relating to various disease states. An important 
note is that the spectral data can be examined as single 
spectra, spectral maps or metabolite images. Typical 
imaging time is 6-12 min. 

Three-dimensional (3D) CSI is similar to CSI but of- 
fers volumetric coverage; this technique can be done in 
true 3D fashion or with multislice 2D approaches. 

Intracranial Tumors and Age of Presentation 

Central nervous system tumors rank second in incidence 
only to lymphoreticular neoplasms during childhood. 
Approximately 15%-20% of all intracranial tumors oc- 
curs in children below 15 years. Most intracranial tumors 
in children represent primary lesions, while cerebral 
metastases are rare. The histologic spectrum of intracra- 
nial tumors and their location in children vary consider- 
ably from those of adults (Table 3). A higher proportion 
of childhood intracranial tumors occurs in the posterior 
fossa where they form the majority of intracranial tumors 
in the 2-10 year age group. Any analysis of intracranial 



tumors must include a consideration of patient age in 
recognition of the most frequent histologies that occur in 
various age groups [1-4, 7, 22]. 

Common Intra-Axial Tumors 

Astrocytoma is the most common primary intra-axial 
mass in the adult population. While there are various 
grading schemes in use throughout the world, the basic 
premise is the same. These tumors range from low-grade 
lesions to highly aggressive malignant neoplasms. The 
differences reflect the degree of cellularity along with the 
presence of mitotic activity, vascular hyperplasia and 
necrosis. These lesions grow by a pattern of infiltration: 
as they infiltrate, they secrete a wide variety of sub- 
stances whose purpose is to promote the survival of the 
tumor cells. Hence they are capable of recruiting their 
own blood supply. As they dedifferentiate, they are seen 
to enhance. If we use the World Health Organization’s 3- 
tier classification scheme, grade I tumors are termed ei- 
ther pilocytic or fibrillary. Grade II tumors are anaplas- 
tic; these have vascular hyperplasia and mitosis. Grade III 
tumors are glioblastoma multiforme; in addition to meet- 
ing the criteria for grade II tumors, they also exhibit 
necrosis. They are so aggressive as to “out-grow” their 
own blood supply [1, 3-5, 9, 23-26]. 

Oligodendrogliomas, as the name implies, take origin 
from oligodendroglia. They are significantly less com- 
mon than astrocytomas, and comprise under 10% of pri- 
mary intra-axial tumors. Typically they are seen to con- 
tain CT-visible calcification in upwards of 80% of cas- 
es. They tend to be located subcortically. As is the case 
with astrocytomas, they also vary from low grade to 
high grade. These tumors, though, tend to have a better 
prognosis as they are somewhat more chemosensitive 
than their pure astrocytic counterparts. They also exist 
in a mixed form, where there are varied proportions of 
oligodendroglial cells and astrocytes. As the degree of 
the oligocomponent increases, so does the prognosis [1, 
3-5, 24-28]. 



Table 3. Common primary intra-axial brain tumors 



Pediatric 


Supratentorial 


Pleomorphic xanthoastrocytoma (PXA) 

Primitive neuroectodermal tumor (PNET) 
Dysembryoplastic neuroectodermal tumor (DNET) 
Ganglioglioma 




Infratentorial 


Juvenile pilocytic astrocytoma 
Primitive neuroectodermal tumor (PNET) 
Brainstem astrocytoma 


Adult 


Supratentorial 


Fibrillary astrocytoma 
Anaplastic astrocytoma 
Glioblastoma multiforme 
Oligodendroglioma 




Infratentorial 


Hemangioblastoma 




E.A. Knopp, W. Montanera 



Gangliogliomas are tumors of a mixed cell population 
taking origin from both glial and neuronal cell lines. 
These are the most common of the so-called mixed tu- 
mors. They tend to be low grade with a good prognosis. 
However, they can be somewhat more aggressive and 
dedifferentiate into higher grade lesions. Typically the pa- 
tient presents with a seizure and is found to have a lesion 
in a cortical location. Most commonly, they are found in 
the temporal lobes. In addition, you can see thinning of 
the overlying bony calvarium, an indicator of the long- 
standing nature of these lesions [1, 3-5, 27]. 

In adults, hemangioblastomas are the most common 
primary infratentorial tumors. They are low grade, essen- 
tially benign neoplasms. Incomplete resection, however, 
can lead to recurrence. Typically they form a cystic mass 
with a solid mural nodule which is highly vascular. The 
cyst wall is not seen to enhance. Their appearance is sim- 
ilar to that of juvenile pilocytic astrocytoma. The princi- 
pal differentiating feature is age. Hemangioblastomas 
tend to present in young, middle-age males (30-40 years). 
They can be multiple, in which case they are typically as- 
sociated with von Hippel-Lindau syndrome [1, 3-5]. 

PNET has been previously referred to as medulloblas- 
toma. However given its primitive nature along with the 
neuroectodermal cell origin, this tumor has been re- 
named. PNET is the most common posterior fossa neo- 
plasm in children. It does, however, have a second peak 
of incidence in adults. While classically occurring in re- 
lation to the cerebellum, PNET does occur in the supra- 
tentorial brain as well. It represents a spectrum of dis- 
eases with a varied degree of aggressiveness, the most ag- 
gressive being the atypical teratoid rhabdoid tumor [1,3- 
5, 7]. 

Juvenile pilocytic astrocytomas or, more commonly, 
pilocytic astrocytomas, classically have been separated 
out from the more infiltrative low-grade astrocytomas. In 
fact, they are histopathologically distinct. They are 
nonaggressive tumors in which gross surgical resection 
should be curative. Their imaging features are a combi- 
nation of low- and high-grade lesions. They are well cir- 
cumscribed yet enhance. Advanced imaging characteris- 
tics (perfusion and spectroscopy) tend to mimic higher 
grade lesions. Thus it is paramount that in this instance 
(and in fact in all instances) the advanced MRI data be 
interpreted along with the conventional images. 
Obviously, the patient’s history helps as well [1, 3-5, 7]. 

By far and away, metastases are the most common 
supratentorial (infratentorial as well) neoplasms in the 
adult. They comprise upwards of 40% of all tumors. 
About half of these lesions are reported to be solitary, 
however, with the use of higher doses of gadolinium (as 
well as higher field strength) this number is decreasing. 
In decreasing order in numbers, they tend to arise from 
lung, breast (in women), melanoma, kidney and gastroin- 
testinal primary tumors. They tend to be located at the 
gray-white junction with a fair amount of vasogenic ede- 
ma (recognized by the sparing of the arcuate fibers along 
with its frond-like appearance). Increased T1 signal can 



mean either melanin or blood products. Mucinous prima- 
ry tumors tend to have low signal on both T2-weighted 
and FLAIR images. Calcification is observed typically 
with lung or breast primary tumor [1, 3-5, 9, 18]. 

Common Extra-Axial Tumors 

Meningioma is the most common extra-axial neoplasm of 
adults. Its incidence is highest in middle-aged women. 
Meningiomas are thought to originate from arachnoid 
cap cells and their distribution parallels that of the cap 
cells that are most abundant in arachnoid granulations. 
The parasagittal and convexity dura, sphenoid ridge, 
parasellar and cerebellopontine (CP) angle are common 
locations. Varying histologic types and varying composi- 
tions lead to some variability of imaging features. 
Meningiomas are usually hyperdense relative to brain on 
CT. Calcification can be detected in roughly 20% of cas- 
es and a bony reaction in the adjacent skull is relatively 
common. If present, this bony reaction usually consists of 
hyperostosis (due to stimulation of a bony reaction with 
or without tumor invasion) and less frequently consists of 
bone destruction. Enhancement on CT or MRI is usually 
relatively homogeneous with occasional cystic compo- 
nents, areas of necrosis, or calcium. Meningiomas have a 
propensity for invasion of dural venous sinuses and en- 
casement of carotid arteries when originating in the cav- 
ernous sinus. When located in the cavernous sinus, 
meningioma can also cause caliber narrowing of the ves- 
sel as well as encasement. Edema in the brain adjacent to 
meningioma is variable and more frequent in larger le- 
sions [2-4, 29, 30]. 

The tern “neurogenic tumor” refers primarily to 
schwannoma and much less commonly to neurofibroma. 
Schwannomas originate from Schwann cells, whose 
myelin processes surround axons of cranial nerves. They 
are most frequently found at the transition zone between 
oligodendroglial and Schwann cell coverings of the ax- 
ons. They originate much more frequently from sensory 
than from motor nerves. Schwannomas represent 6%-8% 
of primary intracranial neoplasms, are more frequent in 
adulthood (peaking in the fifth and sixth decades), and 
are slightly more common in women. Presenting symp- 
toms depend upon the nerve affected. As these tumors are 
well delineated and encapsulated, they affect the cranial 
nerve of origin and adjacent brain by compression rather 
than invasion. The vestibular division of the eighth cra- 
nial nerve is the most frequent origin (internal auditory 
canal and cerebellopontine angle), followed by the fifth 
and seventh cranial nerves. On CT, schwannomas are iso- 
dense or slightly hypodense relative to brain. 
Calcification and hemorrhage are rare. MRI usually 
demonstrates an iso- to hypointense extra-axial mass on 
T1 -weighted sequences, becoming hyperintense on T2- 
weighted sequences. Schwannomas usually enhance in- 
tensely on both CT and MRI. Smaller tumors usually en- 
hance homogeneously, whereas heterogeneity is more 




Brain Tumors 



9 



common in larger tumors due to intralesional necrosis or 
cyst formation. Arachnoid cysts can also be seen in asso- 
ciation with the surface of these lesions. In most cases, 
cerebellopontine angle tumors form acute angles with the 
poms acusticus and the tumor extends into the internal 
auditory canal, often with canal expansion, allowing dis- 
tinction from meningiomas which are also common in 
this location. Schwannomas may affect bony foramina by 
slowly expanding and remodeling them [2-4, 6]. 

Several intracranial mass lesions are not true neo- 
plasms, but are traditionally included among brain tu- 
mors because they represent space-occupying intracranial 
lesions. Dermoids and epidermoids are included in this 
group. Each represents a non-neoplastic “inclusion cyst” 
presumably arising from ectodermal cell rests during em- 
bryogenesis. 

- Epidermoids consist of an ectoderm-derived epithelial 
lining (without ectodermal appendages). As the cyst 
wall desquamates, this material collects within the 
cyst. The cyst slowly expands and insinuates within 
cisternal spaces and fissures. Epidermoids are most 
frequently found off midline and most often in the 
cerebellopontine angle, less frequently around the sel- 
la. Epidermoids may show CT and MRI characteristics 
similar to CSF, and they typically do not enhance fol- 
lowing contrast medium administration. Use of diffu- 
sion-weighted imaging can reliably distinguish these 
lesions from arachnoid cysts. 

- Dermoids are similar inclusion cysts, but their lining 
may also contain ectodermal derived appendages (hair, 
teeth, sweat glands, etc). They are more typically 
found near the midline and may be associated with a 
dermal sinus. Secretions and their breakdown products 
often result in contents that are oily and contain lipid 
metabolites, giving rise to imaging features similar to 
fat. CT usually shows a low density extra-axial mass, 
often with peripheral calcification. Ectodermal ap- 
pendages (hair, teeth, etc.) can contribute to hetero- 
geneity. Although the cyst wall may show some en- 
hancement, the center of the mass should not enhance 
with contrast medium. Dermoids may occasionally 
rupture intracranially and release their oily contents in- 
to the subarachnoid space. The clinical presentation 
may simulate acute subarachnoid hemorrhage and 
imaging demonstrates dispersal of the oily contents in- 
to the subarachnoid space. 

- Other non-neoplastic extra-axial lesions include: 
arachnoid cyst (CSF-filled cavity within arachnoid 
membrane); colloid cyst (anterior third ventricle at 
foramen of Monro); neuroepithelial cyst (most likely 
intraventricular of choroidal origin); and neurenteric 
cyst (cyst wall composed of gut or respiratory epithe- 
lium, remnant of neurenteric canal during embryogen- 
esis) [2-4, 6, 31]. 

Cranial paragangliomas may arise at the jugular fora- 
men (glomus jugulare) or in the middle ear cavity (glo- 
mus tympanicum). These tumors arise from glomus bod- 
ies (neural crest derivatives) and often present with pul- 



satile tinnitus. Glomus jugulare tumors originate in the 
adventitia of the jugular foramen and occlude the jugular 
vein with growth. At the time of diagnosis, there is usu- 
ally infiltration of tumor into the bony margins of the 
jugular foramen with a pattern of permeative bone de- 
struction. CT and MRI show an enhancing soft-tissue 
mass centered on the jugular foramen (jugulare) or infe- 
rior portion of the middle ear cavity (tympanicum). A soft 
tissue component may grow intracranially toward the 
cerebellopontine angle. Highly vascular tumors, these are 
characterized by direct visualization of prominent vessels 
within mass evidenced by MRI flow voids or a “salt and 
pepper” appearance [2-4, 6]. 

Craniopharyngiomas, thought to arise from metaplasia 
of squamous epithelial remnants of Rathke’s pouch, are 
usually centered in the suprasellar cistern. They may ex- 
tend into the sella and retroclival region, or up into the 
third ventricle. Although most common in children, these 
tumors occur scattered throughout the age spectrum. As 
well as their characteristic location, these tumors often 
exhibit cyst formation, calcification, and solid enhancing 
components [2-4, 7, 22, 31]. 

Chordomas arise from remnants of the notochord. 
They are most common in the sacrum. Cranial chordo- 
mas occur almost exclusively in the clivus. They are lo- 
cally aggressive tumors that destroy bone and may grow 
into nasopharynx, parasellar region or prepontine cistern. 
MRI and CT demonstrate an enhancing soft-tissue mass 
centered on the clivus, exhibiting bone destruction and 
areas of calcification. They are almost always hyperin- 
tense on T2-weighted MR sequences and may exhibit in- 
ternal “septations” [2-4, 29]. 

Tumor Follow-up 

Follow-up of patients with intracranial neoplasms tends 
to be dictated by the clinical situation and to fall into two 
general groups: medical and surgical. 

In patients undergoing surgical resection, we perform 
imaging within 24 hours of surgery using routine proto- 
cols. In this timeframe, the postoperative changes affect- 
ing the blood-brain barrier are not manifest and any en- 
hancement is thought to represent residual enhancing tu- 
mor. It is imperative that a noncontrast T1 -weighted im- 
age is obtained, as there can be a fair amount of hyperin- 
tense blood products present. After this, our first conven- 
tional follow-up is 6 weeks later. Scanning between these 
intervals can be fraught with difficulty due to the exu- 
berant contrast enhancement present. Remember, though, 
if the lesion was nonenhancing preoperatively it will not 
enhance in the month following surgery. Further follow- 
up is dictated by the therapeutic protocol the patient is re- 
ceiving. Pure surgical lesions (with gross total resection) 
tend to be followed at 6 weeks, 3 , 6 , 12 and 18 months, 
and then yearly. 

In patients undergoing further medical therapy, precise 
follow-up timing depends upon treatment. Typically in 




10 



E.A. Knopp, W. Montanera 



patients actively receiving chemotherapy, follow-up is be- 
tween 4 and 6 weeks, with courses of chemotherapy in 
between. In this instance, follow-up should include at 
least 1 advanced method (perfusion or spectroscopy) in 
case the therapeutic effect mimics disease progression 
and needs to be differentiated. The same holds true for ra- 
diation therapy. When patients are no longer actively re- 
ceiving aggressive treatment, follow-up occurs in 3- 
month intervals. 

In all instances, the presence of any imaging changes 
with mass effect should prompt further investigation 
with advanced methods. It is also important to realize 
the patterns of tumor spread when looking at follow-up 
images. Primary lesions, being so highly infiltrative, 
spread along paths of less resistance, e.g. along axonal 
bundles and more importantly in a subependymal fash- 
ion. If we have a lesion which is adjacent to the ven- 
tricular system, we must take care to assess the 
subependymal surfaces for subtle linear FLAIR abnor- 
malities tracking around the ventricular system, which 
may eventually enhance as well. Do not assume it’s just 
“white matter disease”. 

When a suspicious finding is made, there are two 
roads to follow: if it is obvious, then it is a tumor recur- 
rence that must be acted upon. If however, you are not 
100% convinced, then closer follow-up in 4-6 weeks is 
warranted [17, 23, 25-28]. 

References 

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693 

2. Altas SW, Lavi E, Golberg HI (2002) Extraaxial brain rumors. 
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3. Grossman RI, Yousem DM (2003) Neoplasms of the brain. In: 
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4. Osborn AG, Rauschning W (1994) Brain tumors and tumorlike 
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123 

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enhanced T2* -weighted MR imaging of recurrent malignant 
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(2002) High-grade gliomas and solitary metastases: differenti- 
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TL, Ehman RL, Forbes GS, Axley PL, Earnest F (1988) 
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Am 37:101-21 




IDKD 2004 



Neuroimaging of Cerebral Vessels; Evidence-based Medicine in the 
Evaluation of Acute Stroke and Aneurysm Detection 

M.E. Jensen 

Interventional Neuroradiology Unit, Department of Radiology, University of Virginia Health Sciences Center, Charlottesville, VA, USA 



Introduction 

As neuroimaging becomes more complex and widely 
available, the cost of health care is rising rapidly for both 
the individual and society as a whole. A continuous flow 
of medical literature makes it difficult to elucidate the 
true science from the merely descriptive. The current 
trend towards evidence-based medicine is an attempt to 
find those diagnostic and therapeutic imaging studies that 
provide the best information at the most reasonable cost. 
The best information comes from randomized controlled 
trials that are prospectively designed to determine perfor- 
mance and efficacy (Level 1 evidence) [1]. It is more 
likely, however, that Level 2 (clinical non-randomized 
studies, cohort and case-controlled studies, uncontrolled 
prospective studies) or Level 3 (descriptive studies, case 
series, expert committee reports) evidence will be more 
readily available. Readers are referred to the recent 
Neuroimaging Clinics of North America monograph [2] 
for more in-depth information. A synopsis of the evi- 
dence-based medicine as it pertains to the neuroimaging 
of common clinical conditions follows here. 



Intracranial Vascular Assessment in the 
Treatment of Acute Stroke 

One of the pitfalls of the NINDS intravenous thromboly- 
sis trial was the lack of information regarding the degree 
and location of vascular occlusion. In a large, randomized 
controlled trial of intra-arterial thrombolysis (PROACT), 
arterial occlusions were demonstrated by digital subtrac- 
tion angiography (DSA) in only 38% of patients with ma- 
jor neurological deficits [3]. Del Zoppo and colleagues 
performed angiography before and after the intravenous 
administration of recombinant tissue plasminogen activa- 
tor (rtPA), and found improved recanalization rates in the 
more distal middle cerebral artery (MCA) branches com- 
pared the internal carotid artery (ICA) [4]. These two 
studies suggested that an intra-arterial approach to large 
proximal thrombi and an intravenous approach to distal 
emboli may be the best therapeutic strategies in acute 



stroke [5]. Reliable imaging information regarding clot 
burden and location must be obtained prior to therapeu- 
tic selection. 

Angiography remains the gold standard in evaluation 
of the arterial tree although it does not define the status 
of the brain parenchyma. It allows evaluation in multiple 
projections, depicts the morphology of the vessel lumen, 
assesses the collateral circulation and visualizes the most 
distal vasculature. The disadvantages include risks of 
stroke and nephrotoxicity, expense, invasiveness, and 
procedural time. 

An advantage of computed tomographic angiography 
(CTA) is that it can be performed immediately after rou- 
tine non-contrast CT, shortening the time to diagnosis 
by eliminating the need to move the patient. Perfusion 
data can be collected at the same time, which may in- 
fluence therapeutic options. CTA images are easy to in- 
terpret and, in my experience, clinician acceptance is 
high. The images are acquired rapidly, so even uncoop- 
erative patients can be scanned. There are disadvan- 
tages, including rapid injection of a large bolus of con- 
trast medium that requires a large-bore intravenous line 
and good renal function. Evaluation of the extracranial 
vessels may also yield important diagnostic and thera- 
peutic information; however imaging the cervical ves- 
sels results in significant intracranial venous opacifica- 
tion that can interfere with interpretation and image re- 
construction [6]. 

Several studies have reported the sensitivity and speci- 
ficity of CTA for detecting occlusions in the circle of 
Willis. Lev et al. [7] recently evaluated the accuracy of 
CTA for the detection of large vessel intracranial throm- 
bus in clinically suspected hyperacute stroke patients. In 
this study, 44 consecutive intra-arterial thrombolysis can- 
didates underwent CTA as part of the imaging protocol. 
Acquisition, reconstruction, and analysis of CTA images 
took approximately 15 minutes. Using axial source and 
maximum intensity projection (MlP)-reformatted im- 
ages, the studies were evaluated for the presence or ab- 
sence of large vessel occlusion. A total of 572 circle of 
Willis vessels were examined; arteriographic correlation 
was available for 224 vessels. Sensitivity and specificity 




12 



M.E. Jensen 



for the detection of large vessel occlusion were 98.4% 
and 98.1%, respectively. Accuracy, calculated using re- 
ceiver operating characteristics analysis, was 99%. Other 
older series have also shown sensitivities and specificities 
of 83%-100% and 99%-100%, respectively, compared to 
DSA [5]. 

The sensitivity and specificity of magnetic reso- 
nance angiography (MRA) is limited compared to that 
of DSA. One study evaluated the reliability of MRA 
source images and MIP images in showing the arterial 
segments of the circle of Willis [8]. MRA source im- 
ages and MIP images were evaluated in 526 arterial 
segments and compared to DSA. MRA MIP images 
had a sensitivity of 87% and a specificity of 88%. 
MRA source images had a sensitivity of 89% and a 
specificity of 63% in depicting the presence of a vessel 
segment. In an earlier study of 50 patients [9], the same 
authors found that MRA had a sensitivity of 100% and 
specificity of 95% for vascular occlusion, and a sensi- 
tivity of 89% and a specificity of 89% for stenosis of 
the intracranial vessels, when compared to DSA. A 
more recent study compared the value of three-dimen- 
sional (3D) time-of-flight (TOP) and phase-contrast 
(PC) MRA for the detection and grading of intracranial 
vascular steno-occlusive disease [10]. Eighteen patients 
were studied with both techniques, and the results were 
compared to those of DSA (performed in 15 patients) 
and transcranial Doppler sonography (TCD). 3D-TOF 
MRA was more specific than 3D-PC MRA (for two 
observers, 87% and 86% vs. 65% and 60%) and had a 
higher ‘negative predictive value (96% vs. 89%). 
Correct grading of stenosis was achieved by 3D-TOF in 
78% of patients and by 3D-PC MRA in 65%. 

Although technical advances in MRA have improved 
the sensitivity and accuracy of this technique in the eval- 
uation of vascular steno-occlusive disease of the brain, 
technical limitations still exist. Relative disadvantages 
include study time when the patient is required to remain 
motionless. Movement may result in slice misrepresenta- 
tion on 2D TOF images and can blur images in all stud- 
ies [6]. In addition, turbulent flow in highly stenosed le- 
sions leads to overestimation of the true lumen size. This 
problem is particularly crucial when surgical decisions 
are to be made using specific operative criteria involving 
the exact measurement of the stenosis. 

In summary, CTA and MRA are currently used to as- 
sess the intracranial vasculature in patients suffering from 
acute stroke. There is some Level 2 and Level 3 evidence 
that shows favorable comparison with DSA in the detec- 
tion of circle of Willis occlusions, particularly for CTA. 
The literature is lacking in the evaluation of smaller 
branches. In addition to providing information about the 
vasculature, these modalities also evaluate the status of 
the brain parenchyma and play a definitive role in the 
evaluation of stroke patients. However, strong evidence to 
support its use as a screening tool for the determination 
of use and delivery method of thrombolytic therapy is 
currently lacking [5]. 



Evaluation of Cerebral Aneurysms 

DSA remains the gold standard in the evaluation of in- 
tracranial aneurysms. As noted before, small but real 
risks are associated with angiography, and a noninvasive 
diagnostic examination would be preferred, if it were 
sufficiently accurate. A meta-analysis of noninvasive 
imaging used to detect intracranial aneurysms was per- 
formed by White and colleagues in 2000 [11]. These au- 
thors analyzed all reports from 1988 to 1998 in which 
10 or more patients were studied and the results were 
compared to DSA. Thirty-eight studies meeting initial 
criteria and scoring greater than 50% on an intrinsical- 
ly weighted standardized assessment were included. The 
rates of aneurysm accuracy for CTA and MRA were 
89% and 90%, respectively. The study showed greater 
sensitivity for aneurysms larger than 3 mm using both 
modalities: for CTA, sensitivity was 96% for aneurysms 
>3 mm and 61% for those <3 mm; for MRA, these val- 
ues were 94% and 38%, respectively. The same authors 
also performed a prospective blinded study comparing 
CTA and MRA to DSA for the detection of aneurysms 
[12]. DSA was performed in 142 patients along with 
CTA and 3D-TOF MRA and all studies were read by 
two observers. The accuracy rates per patient for the 
best observer were 87% for CTA and 85% for MRA. 
The accuracy rates per aneurysm for the best observer 
were 73% for CTA and 67% for MRA. The sensitivity 
of aneurysm detection improved with aneurysms 5 mm 
or larger, to 94% for CTA and 86% for MRA. 
Sensitivities were dramatically diminished with 
aneurysms smaller than 5 mm (57% for CTA and only 
35% for MRA). 

Overall, CTA and MRA show good sensitivity in cas- 
es where aneurysms are 5 mm or larger. Sensitivity drops 
dramatically with smaller aneurysms. Should either 
modality be considered a screening tool for the evalua- 
tion of ruptured and unruptured aneurysms? Using com- 
plex statistical methodology and computer modeling. Van 
Gelder [13] concluded that clinicians can trust a CTA 
finding of a large aneurysm (>6 mm) when subarachnoid 
hemorrhage is present, but the specificity decreases for 
smaller aneurysms (<2 mm). When hemorrhage is pre- 
sent, the likelihood of an aneurysm increases and clini- 
cians can trust CTA findings of both large and small 
aneurysms; however, angiography is warranted in pa- 
tients with hemorrhage and a negative CTA examination. 
When no hemorrhage is present and no aneurysm is 
found at CTA, further evaluation by angiography is less 
warranted than it is in the setting of subarachnoid hem- 
orrhage. 

Technical advances have not been limited to noninva- 
sive imaging alone. In the interpretation and treatment of 
aneurysms, 3D rotational angiography is playing a promi- 
nent role. Three-dimensional images are acquired 
through the use of specialized angiography equipment 
and special reconstructive computer software. With the 
patient isocentered in the C-arm, the C-arm rapidly ro- 




Neuroimaging of Cerebral Vessels 



13 



tates in a 200-degree arc around the patient’s head. 
Acquisition time is approximately 5 s. The first sweep 
provides the data necessary for acquiring the mask im- 
ages. The second sweep is done during the injection of 
contrast medium at a rate of 2. 5-3.0 ml/s for a total of 30- 
35 s. Distortion is automatically corrected. The images 
are sent to a workstation for reconstruction in volume- 
rendered technique; however, source images, maximum 
intensity projection, multiplanar reformatting and sur- 
face-shaded display can also be chosen. 

The information acquired from 3D angiography has 
dramatically improved aneurysm evaluation and treat- 
ment planning. Important information for both endovas- 
cular treatment and surgical clipping is acquired, includ- 
ing the true neck size, morphology of the neck, relation- 
ship of the neck to the surrounding vessels, and visual- 
ization of vessels arising from the neck [14]. This tech- 
nique is not without its disadvantages. Patient movement 
can result in poor image acquisition, and the best images 
are obtained when general anesthesia is used. Low car- 
diac output and poor C-arm reproducibility may also af- 
fect image quality. In addition, the radiation dose to the 
patient’s skin is significant a routine 14-s acquisition de- 
livers a similar dose as an entire biplane cerebral an- 
giogram. Radiation dose is minimized by diminishing the 
acquisition time to 5-8 s. 

Conclusions 

The current movement is towards evaluation of the in- 
tracranial circulation using less invasive therapy. Before a 
technique can replace existing “gold standards,” a body 
of solid evidence-based medicine must exist. To date, 
some data are available to make confident decisions, but 
prospective randomized trials are lacking in many areas. 
To ensure the acceptance of such modalities in the future, 
we are responsible to our patients and to society for pro- 
viding the best possible data from which clinical and fi- 
nancial decisions will be made. 



References 

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evidence-based medicine. Neuroimaging Clin N Am 
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2. Medina LS (ed) (2003) Evidence-based neuroimaging. Neu- 
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3. Furlan A, Higashida R, Wechsler L et al (1999) Intra-arterial 
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in acute ischemic stroke. Neuroimag Clin N Am 13(2).T67- 
183 

6. Phillips CD, Bubash LA (2002) CT angiography and MR an- 
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disease. Radiol Clin N Am 40(4):783-798 

7. Lev MH, Farkas J, Rodriguez VR et al (2001) CT angiography 
in the rapid triage of patients with hyperacute stroke to in- 
traarterial thrombolysis: accuracy in the detection of large ves- 
sel thrombus. J Comput Assist Tomogr 25(4):520-528 

8. Stock KW, Wetzel S, Kirsch E, Bongartz G, Steinbrich W, 
Radue EW (1996) Anatomic evaluation of the circle of Willis: 
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9. Stock KW, Radue EW, Jacob AL et al (1995) Intracranial ar- 
teries: prospective blinded comparative study of MR angiog- 
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10. Oelerich M, Lentschig MG, Zunker P et al (1998) Intracranial 
vascular stenosis and occlusion: comparison of 3D time-of- 
flight and 3D phase-contrast MR angiography. Neuroradiology 
40(9):567-573 

1 1 . White PM, Wardlaw JM, Easton V (2000) Can noninvasive 
imaging accurately depict intracranial aneurysms? A system- 
atic review. Radiology 217:361-370 

12. White PM, Teasdale EM, Wardlaw JM, Easton V (2001) 
Intracranial aneurysms: CT angiography and MR angiography 
for detection prospective blinded comparison in a large patient 
cohort. Radiology 219:739-749 

13. van Gelder JM (2003) Computed tomographic angiography for 
detecting cerebral aneurysms: implications of aneurysm size 
distribution for the sensitivity, specificity and likelihood ratios. 
Neurosurgery 53(3):597-606 

14. Klucznik RP (2002) Current technology and clinical applica- 
tions of three-dimensional angiography. Radiol Clin N Am 
40:711-728 




IDKD 2004 



Evaluation of the Cerebral Vessels 

R. Willinsky 

Toronto Western Research Institute, Clinical Studies Resourse Centre, Toronto, Canada 



Introduction 

In the last decade there has been a dramatic shift to non- 
invasive imaging of the cerebral vessels. This is justified 
since cerebral digital subtraction angiography (DSA) still 
has a risk of neurological complications despite advances 
in techniques and safer contrast agents. Carotid Doppler 
ultrasonography (US) is an excellent screening tool to 
study the carotid bifurcation in patients with transient is- 
chemic attacks and stroke. Transcranial Doppler US is 
useful to detect early vasospasm in patients with sub- 
arachnoid hemorrhage. Multislice computed tomography 
(CT) and magnetic resonance imaging (MRI) have be- 
come effective methods to image the cerebral arteries and 
veins. DSA is now used selectively in treatment planning 
after noninvasive imaging has been used for diagnosis. 

CT Angiography 

With the advent of multislice CT and improved post-pro- 
cessing, CT angiography (CTA) and venography (CTV) 
play important roles in the evaluation of the cerebral ves- 
sels. CTA can be used to evaluate patients with carotid 
stenosis. CTA can detect a hairline residual lumen 
(“string sign”) in patients with near occlusion. Typically, 
the string sign, which was described on DSA, has been 
difficult to show by MRA. 

CTA is a fast and reliable method to evaluate patients 
with subarachnoid hemorrhage. CTA shows most cere- 
bral aneurysms that are detected using DSA. CTA may 
also show thrombosis or calcification in the wall of a 
large or giant aneurysm. Post-processing allows assess- 
ment of the aneurysm with maximum intensity projec- 
tions (MIP) and surface rendered three-dimensional (3D) 
projections in multiple planes (Fig. 1). In many cases, 
CTA is sufficient to allow treatment planning. If the 
aneurysm is unsuitable for endovascular treatment, the 
patient can be treated surgically without the need for 
DSA. In patients with subarachnoid hemorrhage, CTA is 
often more suitable than MRA since patients may be un- 
cooperative. CTA can also be used for aneurysm screen- 



ing in high-risk groups such as those with familial 
aneurysms and polycystic kidney disease. CTV can be 
used to evaluate patients with suspected sinovenous 
thrombosis. 



MR Angiography 

MRA plays a major role in cerebrovascular imaging. 
Gadolinium-enhanced auto-triggered elliptic centric-or- 
dered MRA (ATECO) has superior resolution compared 
to time-of-flight (TOF) MRA. This has been shown in the 
evaluation of the carotid bifurcation and the intracranial 
arteries and veins. MRA to evaluate carotid stenosis has 
eliminated the need for DSA in the majority of patients. 
MRA of the extracranial and intracranial arteries is a 
standard part of the MR evaluation of patients with stroke 
(Fig. 2). Since ATECO is not dependent on the direction 
of flow, this technique gives excellent visualization of 
tortuous vessels and vessels with slow or turbulent flow. 
ATECO can determine if there is an intracranial arterial 
occlusion in patients being evaluated for possible intra- 
arterial thrombolysis. 

MRA is a good technique to screen high-risk individ- 
uals for aneurysms. The ATECO technique is far superi- 
or to TOF MRA since the turbulent flow in an aneurysm 
may not be detected using the TOF method. ATECO is 
useful in detecting neck remnants in patients previously 
treated by coiling. 

ATECO MRV is the imaging modality of choice to 
evaluate the cerebral veins and venous sinuses in patients 
with sinovenous thrombosis. It is far superior to TOF and 
phase contrast methods. In addition, the brain parenchy- 
ma can be assessed at the same time. 



Digital Subtraction Angiography 

Traditionally DSA has been the gold standard to evaluate 
the cerebral vessels. This remains true for the evaluation of 
the cerebral arteries, circulation time and collateral flow. 
This is no longer true for the evaluation of the venous sys- 




Evaluation of the Cerebral Vessels 



15 




Fig. la-e. Incidental aneurysm in a 44- 
year-old woman, a Source image from 
CTA shows a basilar tip aneurysm pro- 
jecting posteriorly, b, c Sagittal and axial 
collapsed MIP images show two lobules 
and the neck of the aneurysm, d, e 
Surface-rendered 3D images (posterior 
and anterior views) from CTA better de- 
fine the relationship of the neck of the 
aneurysm to the parent vessel 




Fig. 2a, b. Normal craniocervical 
ATECO MRA. a Frontal view from 
the aortic arch to the circle of 



Willis, b Post-processing allows better visualization of the posteri- 
or fossa arteries 



tern. ATECO MRV is superior to DSA. Since DSA uses se- 
lective arteriograms, there is washout of the cerebral veins 
and venous sinuses from unopacified blood. In ATECO 
MRV all the veins are opacified equally (Fig. 3). 

DSA allows assessment of the circulation time. This is 
helpful in arterial occlusive disease, arteriovenous shunts, 




Fig. 3. Normal 
ATECO MRV 
gives a robust 
signal from the 
deep and super- 
ficial veins 










16 



R. Willinsky 



venous occlusive disease and the venous congestion re- 
lated to dural arteriovenous fistula with cortical venous 
reflux. In the case of brain micro-arteriovenous malfor- 
mations, the only clue to detect the shunt is the presence 
of an early draining vein. This would be difficult to de- 
tect using CTA or ATECO MRA. 

Collateral flow develops in response to occlusive disease 
in the arteries and veins. Collateral flow and the direction 
of flow are best assessed using DSA. Noninvasive imaging 
with CTA or MRA may detect the presence of a vessel but 
not the direction of flow. Assessment of collateral flow and 
circulation time is important in arterial stenosis and chron- 
ic venous occlusive disease. When venous collaterals en- 
large and become tortuous, they may be evident on nonin- 
vasive imaging. These venous collaterals have been referred 
to as the pseudophlebitic pattern on DSA. 

CTA and MRA are now used extensively to diagnosis 
cerebral aneurysms. Rotational DSA with 3D reconstruc- 
tion gives the best details of the morphology of the 
aneurysm and the adjacent vessels (Figs. 4, 5). Rotational 



Fig. 5. Transparent shad- 
ing of a 3D image from 
right internal carotid rota- 
tional DSA. Note the ante- 
rior communicating aneur- 
ysm {arrow) and duplica- 
tion of the anterior commu- 
nicating artery 



DSA may reveal an aneurysm not evident on standard 
DSA projections. Treatment planning of complex and 
wide neck aneurysms is best determined after analysis of 
the rotational DSA and 3D reconstruction. 





h 



Fig. 4a, b. Surface-ren- 
dered 3D images from right 
internal carotid rotational 
DSA. a Frontal view shows 
an aneurysm at the accesso- 
ry middle cerebral artery bi- 
furcation. b Posterior view 
shows that the branch arises 
from the aneurysm 




Cavernous Malformations 

Cavernous malformations (CMs), or cavernomas, are 
vascular malformations of the central nervous system 
composed of well-circumscribed sinusoidal vascular 
channels containing blood in various stages of thrombo- 
sis. They affect 0.4%-0.9% of the general population ac- 
cording to large autopsy studies. They constitute 5%-16% 
of all vascular malformations. Multiple lesions are found 
in 17%-54% of patients, and in 50%-85% of these cases 
the multiple CMs are familial (autosomal dominant). 
Cavernous malformations often present in the second to 
fifth decades. Presentation includes seizures (31% of cas- 
es), hemorrhage (18.4%) and focal neurologic deficits 
(15%); the rest are incidental. 

Developmental venous anomalies (DVAs) are associat- 
ed with CMs. DVAs represent an extreme variant of the 
normal venous drainage. DVAs drain normal brain and 
must be preserved when CMs are excised. On MRI, CMs 
appear as radiating, linear flow voids (a “caput medusa” 
pattern) centered on a large collecting vein. 

MRI is the diagnostic tool of choice for detecting and 
identifying cavernous malformations. On noncontrast 
CT, CMs frequently appear as focal areas of increased 
density within the brain often without mass effect. The 
differential diagnosis on CT includes low grade calcified 
neoplasms, hemorrhage and vascular malformations. The 
characteristic MRI appearance is a well-defined, lobulat- 
ed lesion with a reticulated core of heterogeneous signal 
intensity on both Tl- and T2-weighted sequences result- 
ing from thrombosis, fibrosis, calcification and hemor- 
rhage. On T2-weighted or gradient echo images, there is 
a peripheral ring of hypointensity that corresponds to the 
deposition of hemosiderin in the surrounding brain 
parenchyma. Cavernous malformations are angiographi- 
cally occult. 





Evaluation of the Cerebral Vessels 



17 



In cases where a CM is suspected but the radiologic 
image is not pathognomonic, serial imaging is of value if 
immediate surgical intervention is not warranted. 
Differential diagnoses include neoplasms and 
hematomas. If there is a recent bleed or thrombosis in a 
CM, the typical features of a CM may not be evident. 
Perilesional and extralesional hemorrhage may be evident 
outside the hemosiderin ring. 

Dissection of the Extracranial Cervical 
Arteries 

Dissection of the carotid or vertebral artery can be spon- 
taneous or traumatic. Spontaneous dissections of the 
carotid or vertebral artery account for 2% of all ischemic 
strokes but in young and middle-aged patients they ac- 
count for 10%-25% of cases. Spontaneous dissections oc- 
cur in all ages but there is a peak incidence in the fifth 
decade. 

Dissections are more common in patients with herita- 
ble connective tissue disorders including Ehlers-Danlos 
syndrome type IV, Marfan’s syndrome, polycystic kidney 
disease and osteogenesis imperfecta. Angiographic 
changes of fibromuscular dysplasia are found in 1 5 % of 



patients with spontaneous dissections of the carotid or 
vertebral artery. Bilateral dissections, either carotid or 
vertebral, are not rare (Fig. 6). 

Dissections of the carotid or vertebral artery arise from 
a tear of the intima. The intramural hematoma may be 
subintimal or subadventitial. The typical patient with 
carotid dissection presents with pain on one side of the 
face or neck, a partial Horner’s syndrome (miosis, ptosis) 
and the delayed onset of stroke. Patients with vertebral 
dissection often have pain in the back of the neck, an oc- 
cipital headache and the delayed onset of posterior fossa 
ischemic symptoms. A lateral medullary syndrome 
(Wallenberg’s syndrome) is a commonly found. 

DSA has been the traditional diagnostic test to detect 
a dissection. Definitive signs of dissection are the pres- 
ence of two lumens or demonstration of an intimal flap. 
Indirect signs are more commonly seen and include a 
long, irregular tapered stenosis, long tapered occlusion, 
or a dilatation (pseudoaneurysm) with a proximal steno- 
sis. Carotid dissections tend to start beyond the bulb and 
often stop at the skull base. Vertebral dissections often 
occur at the C1-C2 vertebral levels and may be extend in- 
to the intradural segment. 

MRI is replacing DSA as the primary investigation of 
carotid or vertebral artery dissections. MRI can show the 



a 



c 




Fig. 6a-d. Bilateral internal carotid and right vertebral artery dissections in a 44-year-old 
woman who presented with a posterior fossa stroke, a, b Axial source images from CTA show an 
aneurysm of the right vertebral artery (arrow in a) and an intimal flap in the right internal carotid 
artery (arrow in b). c ATECO MRA shows bilateral internal carotid aneurysms and the right ver- 
tebral artery aneurysm (arrows), d 3D image from right vertebral rotational DSA shows an ir- 
regular, fusiform aneurysm just beyond the right posterior inferior cerebellar artery 





18 



R. Willinsky 



intramural hematoma especially if fat saturation tech- 
niques are used. ATECO MRA can be used to clarify the 
extent of the abnormality and to detect pseudoaneurysms. 

Dissection of the Intracranial Arteries 

Intracranial dissections are often spontaneous and may 
present with subarachnoid hemorrhage or stroke. The 
commonest location is the intradural vertebral artery. 
Other common sites include the proximal posterior cere- 
bral artery and the proximal posterior inferior cerebellar 
artery. Patients who present with hemorrhage have high 
risk for re-bleeding. Noninvasive imaging may reveal an 
aneurysm or a long irregular stenosis. DSA is critical for 
diagnosis and treatment planning. DSA often shows an 
irregular fusiform dilatation with a stenosis proximal to 
the dilatation. Assessment of collateral flow is critical 
since treatment often involves sacrifice of the diseased 
segment. 

Cerebral Sinovenous Thrombosis 

The clinical presentation of cerebral sinovenous throm- 
bosis (CVT) is closely related to the location and the ex- 
tent of the thrombosis (cortical vs. dural sinus, superfi- 
cial vs. deep). The clinical sequelae of CVT are related to 
the temporal evolution of the disease, the patient’s venous 
anatomy and the effectiveness of collateral venous path- 
ways. The most frequent symptoms and signs of CVT are 
headaches, vomiting, and papilledema reflecting in- 
creased cerebral venous pressure. Patients may go on to 
develop seizures, decreased level of consciousness or fo- 
cal neurologic deficit. Tissue damage and stasis (trauma, 
surgery and immobilization), hematologic disorders (pro- 
teins C and S deficiencies; increased resistance to acti- 
vated protein C), malignancies, collagen vascular disease 
(systemic lupus erythematosus, Behget’s syndrome), 
pregnancy and some medications (oral contraceptives, 
hormone replacement therapy, corticosteroids) are pre- 
disposing factors for CVT. 

Imaging findings of CVT can be categorized as direct, 
when there is visualization of cortical or dural sinus 
thrombus, or indirect when there are ischemic changes 
related to the venous outflow disturbance. Thrombus 
within the dural sinus or cortical vein can be identified as 
an elongated high-attenuation lesion on nonenhanced CT 
{cord sign). If the thrombus is located in the superior 
sagittal sinus, then a triangular filling defect {empty delta 
sign) can be demonstrated on post-contrast images. MRI 
is the modality of choice in dural sinus thrombosis. Acute 
thrombus is isointense to brain on T1 -weighted images 
and hypointense on T2-weighted images. From 3-7 days 
after thrombus formation, the clot on MRI becomes hy- 
perintense on T I -weighted images. The combination of 
MRI and ATECO MRV allows for an accurate diagnosis 
of CVT. 



Venous infarction may be evident on CT as a diffuse, 
low-attenuating lesion. Mass effect is common and 40% 
of symptomatic patients show CT evidence of hemor- 
rhage. Bilateral, parasagittal, hypoattenuating lesions on 
CT is a common feature of venous thrombosis in the su- 
perior sagittal sinus. These lesions do not conform to an 
arterial distribution but do involve the cortex. Isolated in- 
volvement of the temporal lobe is common and found in 
CVT of the transverse sinus. Bilateral thalamic hypoat- 
tenuating lesions on CT may be evident in deep venous 
thrombosis and, on noncontrast CT, thrombus may be 
seen in the straight sinus. 

MRI is sensitive to the parenchymal changes in CVT. 
Cortical and subcortical high signal intensity lesions on 
FLAIR and T2-weighted images are highly suggestive of 
CVT when the lesions do not correspond to an arterial 
territory. Restricted diffusion in CVT may not have the 
same prognostic value as it does in arterial stroke and 
there may be reversibility of venous ischemia in CVT. 
This correlates with the important clinical improvement 
that may occur after an initial major neurological deficit 
related to CVT. 



Intracranial Dural Arteriovenous Fistulas 

Dural arteriovenous fistulas (DAVFs) represent 10%- 
15% of all intracranial arteriovenous lesions. They con- 
sist of one or more true fistulas, direct arteriovenous con- 
nections without an intervening capillary bed, localized 
within the dura mater. DAVFs have been categorized as 
either benign or aggressive based on their venous 
drainage and clinical symptoms. Benign DAVFs drain in- 
to the dural sinuses only, whereas aggressive DAVFs have 
reflux into the cortical veins. Non-hemorrhagic neuro- 
logical deficits, hemorrhage and death are considered ag- 
gressive, while chronic headache, pulsatile bruit and or- 
bital symptoms including cranial nerve deficit due to cav- 
ernous sinus lesions (ophthalmoplegia) are considered 
benign. Aggressive DAVFs have an annual risk of in- 
tracranial hemorrhage or non-hemorrhagic neurological 
deficits of 8.1% and 6.9% respectively, adding up to a 
15.0% annual event rate. Aggressive DAVFs must be 
treated whereas the benign DAVFs may not require treat- 
ment if the symptoms are stable and well tolerated. 

The term venous congestive encephalopathy describes 
a condition of cranial neurological deficits caused by ve- 
nous hypertension secondary to cortical venous reflux 
from a DAVE This entity is analogous to the venous con- 
gestive myelopathy of the spinal cord in the presence of 
a spinal DAVF. On MRI, T2 hyperintensity in the 
parenchyma can be seen as a result of the venous hyper- 
tension and passive congestion of the brain. In the cere- 
bral and cerebellar hemispheres, the deep white matter 
seems to be the most vulnerable to this phenomenon; af- 
ter treatment these findings may be partially reversible. 
The differential diagnosis of the T2 hyperintensity in- 
cludes a superior sagittal sinus thrombosis with a venous 




Evaluation of the Cerebral Vessels 



19 



infarction or venous congestion, demyelination or dys- 
myelination. In the cerebellum, a peripheral diffuse en- 
haneement pattern surrounding the central T2 hyperin- 
tensity is characteristic of DAVFs with cortical venous 
reflux. The combination of central T2 hyperintensity with 
a surplus of pial vessels is highly suggestive of a vascu- 
lar malformation and mandates prompt DSA. 

Moyamoya Disease 

Moyamoya disease is a primary vascular disease charac- 
terized by progressive stenosis and eventual occlusion of 
the supraclinoid portion of the internal carotid artery and 
the adjacent segments of the middle and anterior cerebral 
arteries. In response, an abnormal vascular network of 
small collateral vessels develops to bypass the area of oc- 
clusion. This disease affects children as well as adults. 
Adults tend to present with hemorrhage. The most fre- 
quent symptoms in children are multiple transient is- 
chemic attacks and some episodes result in a fixed 
deficit. Seizures are a common presentation of patients 
under the age of six years. The disorder is often progres- 
sive resulting in a severe motor impairment and intellec- 
tual deterioration. The small collateral vessels at the base 
of the brain are enlarged lenticulostriate vessels. These 
collaterals may be evident on MRI and on DSA represent 
the “puff of smoke” appearance characteristic of this dis- 
ease. DSA may reveal transdural anastomoses and collat- 
eral pial vessels crossing the watershed territories. 

Central Nervous System Vasculitis 

Central nervous system (CNS) vasculitis is inflammation 
of blood vessel walls that results in symptoms by causing 
ischemia. Vasculitis affecting the CNS alone is referred 
to as primary angiitis of the CNS. Secondary vasculitis 
occurs in association with a variety of conditions, in- 
cluding infections, drug abuse, lymphoproliferative dis- 
ease and connective tissue diseases. The pathogenesis of 
vasculitis includes different immunological mechanisms. 
A wide spectrum of clinical features may occur. The typ- 
ical clinical presentations of CNS vasculitis are stroke, 
encephalopathy and seizures. 

MRI findings suggestive of vasculitis are multiple, bi- 
lateral lesions in the cortex and white matter. The pres- 
ence of gray matter involvement should help differentiate 
the white matter lesions from demyelination. In approxi- 
mately 20% of proven cases, DSA shows abnormalities 
in the cerebral arteries including segmental narrowing, 
microaneurysms and vascular beading. The findings may 
be similar to atherosclerosis, vasospasm and infection. 
DSA results must be interpreted in conjunction with the 
clinical and laboratory results. 



Suggested Reading 

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tive evaluation of carotid artery stenosis: elliptic centric con- 
trast-enhanced MR angiography and spiral CT angiography 
compared with digital subtraction angiography. AJNR Am J 
Neuroradiol 24:1012-1019 

Anderson GB, Findlay JM, Steinke DE, Ashforth R (1997) 
Experience with computed tomographic angiography for the 
detection of intracranial aneurysms in the setting of acute sub- 
arachnoid hemorrhage: clinical study. Neurosurgery 41:522- 
528 

Farb R, Scott JN, Willinsky R, Montanera W, Wright G, terBrugge 
K (2003) Intracranial venous system: gadolinium-enhanced 
three-dimensional MR venography with auto-triggered elliptic 
centric-ordered sequence - initial experience. Radiology 
226:203-209 

Fieschi C, Rasura M, Anzini A, Beccia M (1998) Central nervous 
system vasculitis. J Neurol Sci 153:159-171 
Gladstone D, Silver F, Willinsky RA, Tyndel F, Wennberg R (2001) 
Deep cerebral venous thrombosis: an illustrative case with re- 
versible diencephalic dysfunction. Can J Neurol Sci 28:159-162 
Hirai T, Korogi Y, Suginohara K et al (2003) Clinical usefulness of 
unsubtracted 3D digital angiography compared with rotational 
digital angiography in the pretreatment evaluation of intracra- 
nial aneurysms. AJNR Am J Neuroradiol 24:1067-1074 
Lazinski D, Willinsky RA, terBrugge K, Montanera W (2000) 
Dissecting aneurysms of the posterior cerebral artery: an- 
gioarchitecture and review of the literature. Neuroradiology 
42:128-133 

Lee SK, terBrugge K, Willinsky R, Montanera W (2003) MR 
imaging of dural arteriovenous fistula draining into cerebellar 
cortical veins. AJNR Am J Neuroradiol 24:1602-1606 
Lev MH, Romero JM, Goodman DNF et al (2003) Total occlusion 
versus hairline residual lumen of the internal carotid arteries: 
accuracy of single section helical CT angiography. AJNR Am 
J Neuroradiol 24:1 123-1 129 

Rivera P, Willinsky R, Porter P (2003) Intracranial cavernous mal- 
formations. Neuroimaging Clin N Am 13:27-40 
Schievink WI (2001) Spontaneous dissection of the carotid and 
vertebral arteries. N Engl J Med 344:898-906 
Van Dijk M, terBrugge K, Willinsky RA, Wallace C (2002) The 
clinical course of cranial rural AV fistulas with long-term per- 
sistent cortical venous reflux. Stroke 33(5): 1233-1236 
Van Dijk JMC, Willinsky R (2003) Venous congestive en- 
cephalopathy related to cranial dural arteriovenous fistulas. 
Neuroimaging Clin N Am 13:55-72 
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parative study of CT venography with intrarterial digital sub- 
traction angiography. AJNR Am J Neuroradiol 20:249-255 
Willinsky RA, Taylor SM, ter Brugge K, Montanera W, Farb R 
(2003) Neurologic complications of cerebral angiography: a 
prospective analysis of 2899 procedures. Radiology 
227(2):522-528 

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Willinsky RA, Goyal M, terBrugge K, Montanera W (1999) 
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IDKD 2004 



Imaging and Management of Acute Stroke 

W.T.C. Yuh‘, T. Taoka2, T. Ueda^, M. Maeda^ 

^ University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; ^ Department of Radiology, Nara Medical University, 
Kashihara, Japan; ^ Department of Neurosurgery, Yokohama Stroke and Brain Center, Isogo-ku, Yokohama, Japan; Department of 
Radiology, Mie University School of Medicine, Tsu, Mie, Japan 



Introduction 

With recent advances in both imaging techniques and 
reperfusion therapies, patients with acute stroke now have 
a realistic window of opportunity for effective interven- 
tion and treatment outcome. It is generally believed that 
“time is brain,” i.e. the maximum benefit can only be 
achieved when intervention is initiated within the first 3- 
6 hours after the onset of symptoms, depending upon the 
treatment (e.g. intravenous administration of tissue plas- 
minogen activator or endovascular recanalization). 

Since the US Food and Drug Administration (FDA) ap- 
proved the intravenous administration of tissue plasmino- 
gen activator (tPA) for stroke therapy in 1996, there has 
been only a limited overall impact (estimated <1%) to 
stroke victims [1]. This limited impact of tPA has been 
mostly attributed to two major factors. First, there is a rela- 
tively low rate of recruitment of eligible patients, likely due 
to the relatively short therapeutic windows for both intra- 
venous (3 hours) and endovascular (6 hours) recanalization. 
Second, there is a relatively low rate of therapeutic efficacy 
(12%-30%) as reported by the recent intravenous throm- 
bolysis trial, likely due to the lack of an effective and vali- 
dated strategy for patient selection [1-3]. Despite the po- 
tential benefits of both intravenous (tPA) and endovascular 
recanalization procedures, to date only about 1% and 16% 
of patients are eligible for treatment based upon the con- 
ventional 3- and 6-hour therapeutic windows, respectively. 

Currently, stroke patients seek medical attention an av- 
erage of 13 hours after the onset of symptoms. This means 
that the vast majority do not have an opportunity to bene- 
fit from thrombolytic therapy as currently prescribed. The 
Stroke Council of the American Heart Association (AHA) 
is increasing its efforts to educate the general public in 
both the recognition of early signs and symptoms of acute 
stroke, as well as the need to seek immediate medical at- 
tention. The expectation is to significantly increase the 
number of potentially eligible patients up to 20% [4]. 
Although the AHA expects that the average time at which 
patients seek medical attention will shorten, realistically 
most patients still will not be eligible for intravenous or in- 



tra-arterial revascularization interventions unless there are 
ways to identify a subgroup of patients with a therapeutic 
window longer than the presumed 3 or 6 hours. Therefore, 
there is a need to apply these useful imaging parameters in 
triaging patients who may be at risk for reperfusion hem- 
orrhage or who are likely to benefit from arterial reperfu- 
sion within or beyond the traditional therapeutic window. 

Therapeutic Window after Ischemic Stroke 

The true therapeutic window for effective outcome after 
revascularization in ischemic stroke in humans remains 
to be defined. Based on both experimental and clinical 
studies, some have suggested that the maximal time for 
achieving best treatment outcome after revascularization 
in the setting of acute stroke is within the first 6 hours af- 
ter onset of symptoms [5]. This was first confirmed clin- 
ically by Zeumer et al. [6] who observed that intra-arter- 
ial thrombolytic therapy used in the treatment of acute in- 
ternal carotid artery or middle cerebral artery occlusion 
was best performed within 5 hours of symptoms onset. 
Recently, our group retrospectively evaluated 42 lesions 
in 30 patients and underwent successful recanalization 
within the first 12 hours of symptoms [7]. Similar to 
Zeumer et al.’s work, our study suggested that a 5-hour 
therapeutic window may be preferable. These studies are 
consistent with animal experiments that measured the re- 
lationship between the severity and duration of ischemia 
(Fig. la). Interestingly, our study also suggested that 
within the first 5 hours of onset of symptoms, the thera- 
peutic outcome was dependent upon the severity and du- 
ration of ischemia (Fig. lb). However, our findings also 
pointed out that, after the 5 -hour period of ischemia, 
residual cerebral blood flow appeared to be the most im- 
portant factor that influenced therapeutic outcome. 

Despite conventional wisdom, several studies have 
provided evidence for an extended therapeutic window up 
to 36 hours from onset of symptoms [7-1 1]. In particular, 
it is well known that the effective therapeutic window for 
revascularization of posterior circulation of ischemia is 




Imaging and Management of Acute Stroke 



21 



Ischemia Thresholds 




TIME 



tf/h J 19SI 




Time, h 



o Non*infarclion 
o Infarction 
• Hemorrhage 



Fig. la, b. The relationship between ischemia severity (as determined by the ratio of ischemic regional activity to cerebellar activity, R/CE) 
and duration a Animal study (reproduced from [15] with permission) b Our preliminary data from perfusion imaging in human s (repro- 
duced from [7] with permission) 



often relatively longer compared to that of the anterior 
circulation [12, 13]. Conversely, both intravenous and in- 
tra-arterial thrombolytic therapies may not always be as- 
sociated with satisfactory outcomes despite achieving 
successful recanalization within the conventional 3- or 6- 
hour therapeutic window. This is often attributed to hem- 
orrhagic complications by reperfusing the ischemic core 
or a probable lack of reversibility of the ischemic tissue 
that is located in an eloquent area of the brain. 

Cerebral Blood Flow and Assessment of 
Tissue Viability and Ischemic Reversibility 

Cerebral blood flow (CBF) of the normal brain ranges 
from 45 to 1 10 ml per minute 100 grams tissue, varying 
both in time and location within the same individual 
(Fig. 2a) [14-17]. Below-normal CBF may be broadly 



defined as hypoperfusion that includes a range of values 
arbitrarily defined as oligemic and ischemic. Cerebral 
oligemia is associated with underperfused brain 
parenchyma that will spontaneously recover, and is more 
likely to not be associated with overt neurological symp- 
toms. In contrast, ischemic range reduction of CBF is 
typically symptomatic and at risk for irreversible infarc- 
tion if revascularization does not occur. This includes 
both the core region of CBF reduction as well as the 
larger surrounding area of so-called penumbra. Animal 
studies have shown that an ischemic threshold, defined 
as cessation of normal action potential generation, oc- 
curs at approximately 20 ml x min~' 100 g”'. For infarc- 
tion threshold, i.e. the point of irreversible ischemic in- 
jury to neurons, the reduction of CBF has been estimat- 
ed at approximately 10 ml x min"' 100 g”*. 

It is believed that the ischemic penumbra constitutes a 
potentially reversible volume of cerebral tissue that has 




Ischemic 

iniurv 



Outcome of Ischemia 


b 


with Early Keeanalization 




-► 


Recover 






* -> 


Infarction 


— — ► 


Hemorrhage 



Recanalization ( ) less severe ( ) 



Fig. 2. Definitions and terminology (a) related to various ranges of CBF, and their significance (b) related to the ischemic injury (viabil- 
ity and reversibility) prior to and after treatment 





22 



W.T.C. Yuh, T. Taoka, T. Ueda, M. Maeda 



CBF between the ischemic and infarction thresholds 
mentioned previously [16, 18-20]. The existence of this 
ischemic penumbra has been suggested by perfusion and 
diffusion imaging studies of untreated patients [21-23]. 
However, without timely successful recanalization, the 
penumbra eventually progresses to irreversible infarction 
that cannot be differentiated from core areas of ischemia 
detected in earlier phases of stroke. Interestingly, al- 
though the classic range of CBF for ischemic penumbra 
is between 10-20 ml x mirr^ 100 g“^ in animal studies 
(Fig. la) [15], clinical studies have shown that this region 
of potentially reversible ischemia depends on time and 
anatomic location, and varies in individual patients. This 
suggests that an absolute measurement of CBF may not 
be necessary for determining potential viability and re- 
versibility during emergent triage of a stroke patient [11, 
24, 25]. This has led our group to apply semiquantitative 
and relative measurements of residual cerebral blood 
flow for the purposes of rapid determination of potential 
salvage ability (reversibility) and risk of hemorrhage (vi- 
ability) in the setting of acute stroke intervention. 

Hemorrhagic complications associated with both 
spontaneous and therapeutic arterial revascularization in 
the setting of acute stroke are believed to be related to 
reperfusion injury within the microvascular bed of non- 
viable brain tissue (Fig. 2b). Theoretically, ischemic 
brain that has adequate collateral circulation may remain 
viable long enough so that revascularization will not re- 
sult in reperfusion injury and consequent hemorrhagic 
complication. Ischemic brain that remains viable at the 
time of revascularization may be salvageable (i.e. re- 
versible) if successful and timely reperfusion is 
achieved. However, it is also possible that brain tissue 
that is viable at the time of attempted revascularization 
may have actually suffered irreversible ischemic injury 
that progresses to infarction. In this setting, early reper- 
fusion is associated with low risk of hemorrhage despite 
the progression to infarction. 

The concepts of temporal viability and ischemic re- 
versibility can only be properly assessed in a setting of 
demonstrated early recanalization, such as commonly 
achieved with intravenous and intra-arterial thrombolysis. 
Amazingly, most prior studies have only evaluated un- 
treated patients. We have taken the approach of assessing 
relative differences in residual CBF estimated with Tc99- 
HMPO single photon emission computed tomography 
(SPECT). Our preliminary data suggest that in patients 
who have undergone successful recanalization, the CBF 
thresholds for viability and reversibility are approximate- 
ly 35% and 55%, respectively (when compared to normal 
brain parenchyma) (Fig. lb) [7]. Our study also demon- 
strated that most hemorrhages (71%) occurred during 
early therapeutic intervention (3-5 hours) in patients with 
low residual CBF (below 35%). These findings suggest 
that the conventional time window alone cannot differen- 
tiate between patients at low and high risk for reperfusion 
hemorrhage. Instead, it appears that the pretreatment 
residual CBF may differentiate three categories of treat- 



ment outcomes for ischemic lesions. These can be con- 
veniently categorized as: (i) hemorrhage, (ii) infarction, 
and (iii) reversible ischemia (Fig. lb). Another interesting 
observation from our preliminary data is that certain is- 
chemic insults with relatively high residual CBF may be 
successfully salvaged up to 12 hours after the onset of 
symptoms. Finally, it should be noted that the viability 
threshold of CBF reduction found with SPECT is similar 
what we observed using perfusion magnetic resonance 
imaging (MRI) in an untreated group of patients with 
acute stroke [26]. 



Neuroimaging in Acute Stroke 

Neuroimaging techniques have made significant im- 
provements in stroke imaging, particularly for early de- 
tection and delineation of acute ischemia. This has been 
almost exclusively based upon observations of untreated 
patients [21, 27-42]. Currently, there is no reliable and 
definitive pretreatment imaging means to identify indi- 
viduals who are at risk for hemorrhagic complications or 
those who will potentially benefit by early restoration of 
CBF [1]. 

Diffusion- weighted imaging (DWI) has a sensitivity of 
88%-100% and a specificity of 95%-100% in the diag- 
nosis of acute stroke [27-36]. DWI may be positive as 
early as 30 minutes after the onset of symptoms [37]. 
This capability is essential for the early confirmation and 
delineation of acute ischemia and to facilitate early ther- 
apeutic intervention [21, 37-42]. The efficacy of DWI in 
the assessment of tissue viability and reversibility, partic- 
ularly for considering early intervention, has not been es- 
tablished [25, 26, 43-46]. Abnormal diffusion measure- 
ments in the setting of acute stroke may consist of early 
intracellular and extracellular changes in water distribu- 
tion associated with both reversible and irreversible cere- 
bral ischemia [46]. The ischemic lesion volume and ap- 
parent diffusion coefficient (ADC) values measured by 
diffusion MRI may have predictive value for clinical out- 
come in untreated patients [47, 48]. However, Baird and 
Warach [49] have argued that there is no absolute thresh- 
old of ADC decrease that predicts evolution to infarction. 
Furthermore, diffusion abnormalities in the setting of 
acute stroke may be reversible if early reperfusion occurs 
[21, 29, 43, 44, 50]. It is likely that DWI only indirectly 
reflects the severity of hypoperfusion, as supported by the 
lack of a linear relationship between the magnitude of 
ADC reduction and degree of ultimate ischemic injury 
[50, 51]. Furthermore, the apparent threshold of CBF re- 
duction needed to produce abnormalities on DWI is high- 
er than the experimentally defined ischemic and infarc- 
tion thresholds [52, 53]. Diffusion abnormalities are like- 
ly to represent a summation of changes from cellular dys- 
fimction over a period of time [53, 54]. This suggests that 
DWI is sensitive in detecting ischemia but may not be as 
specific as perfusion imaging for the assessment of via- 
bility and reversibility [43, 44, 55, 56]. 




Imaging and Management of Acute Stroke 



23 



Perfusion MRI provides more direct information relat- 
ed to aberrations in regional CBF that may be more re- 
flective of the primary underlying pathophysiology of an 
acute ischemic insult. Although at present perfusion MRI 
cannot produce absolute values of CBF, it is capable of 
making semiquantitative estimates of relative mean tran- 
sit time (rMTT), relative cerebral blood volume (rCBV), 
and relative CBF (rCBF) that can be mapped to the cere- 
bral anatomy These maps can be generated quickly, hav- 
ing already been proven to be feasible and valuable in de- 
cision making for acute stroke intervention [26, 45, 57]. 
Based upon the dynamic contrast enhancement curve, a 
flow-related map can be generated by various parameters 
(e.g. mean transit time, peak time) and a blood volume 
map can be estimated. The relationship between the CBF, 
MTT and CBV can be expressed as the following: 
rCBF = rCBV / rMTT 

The increased signal intensity on the flow-related 
maps such as the rMTT map is equivalent to an increased 
vascular resistance as seen in Ohm’s law (V=IR), if we 
consider relative CBF to be equivalent to current (I) and 
rCBV equivalent to voltage (V). An increase of signal in- 
tensity on the rMTT map may not indicate ischemia or in- 
farction, as seen in patients with asymptomatic carotid 
stenosis or occlusion. Therefore, flow-related maps such 
as the rMTT map only suggest increased vascular resis- 
tance [58-60] and are less ideal than rCBV and rCBF 
maps in the assessment of ischemic viability and re- 
versibility, as frequently done in the past. 

A recent report suggested that the combined use of 
perfusion imaging and DWI may be beneficial in moni- 
toring the efficacy of thrombolytic therapy [61]. Our 
group has reported that ischemic tissues with prolonged 
rMTT and a marked decrease in rCBV tend to suffer ir- 
reversible ischemic injuries [62]. A mild decrease in 
rCBV with prolonged rMTT suggests that it is possible to 
differentiate between severely ischemic tissue and peri- 
infarct parenchyma by rCBV maps in hyperacute is- 
chemia [63]. Using the combination of perfusion and dif- 
fusion measurements in untreated patients, others have 
suggested that significant mismatching of perfusion and 
diffusion abnormalities may serve as a basis for selecting 
patients who are most likely to benefit from therapeutic 
revascularization [23, 64]. However, such an approach 
has certain theoretical limitations that require further 
evaluation, and also require proper validation when ap- 
plied to an appropriate patient population. There are sev- 
eral reasons for this. First, the observations of these stud- 
ies are mostly based upon an untreated population of pa- 
tients that may not be representative (in terms of demo- 
graphics, clinical status and, possibly, pathophysiology) 
of patients being prospectively considered for acute ther- 
apeutic intervention. Second, these studies utilized rMTT 
mapping, which is highly sensitive to any homodynamic 
compromise that produces a state of hypoperfusion. 
However, as stated earlier, increased rMTT can be 
likened to a relative increase in vascular resistance, which 
can occur in various settings of acute-subacute ischemia 



or chronic oligemia [62]. Therefore, this type of perfu- 
sion mapping cannot differentiate the time of onset of the 
resistance or functional significance of a given rMTT ab- 
normality, which in our experience is not always indica- 
tive of ischemia. Third, the size and magnitude of hyper- 
intensity in rMTT maps are highly dependent upon the 
proximity and severity of vascular narrowing, respective- 
ly, which again does not always translate to actual is- 
chemia. For example, a proximal stenosis of a major cere- 
bral artery is more likely to produce a larger area of ab- 
normal rMTT than an occlusion of a more distal branch 
within the same territory. Finally, since the CBF reduc- 
tion threshold for producing positive findings on both 
diffusion imaging and rMTT maps is likely much higher 
than the “true” ischemia and infarction thresholds, qual- 
itative assessments alone of DWI and rMTT may overes- 
timate the severity of ischemic injury in a given patient, 
which would result in denying some patients the poten- 
tial benefit of thrombolytic therapy [51, 52]. We believe 
that better patient selection for thrombolytic therapy will 
eventually be possible by assessing cerebral ischemic vi- 
ability and reversibility using more quantitative compar- 
isons of diffusion abnormalities with both rMTT and 
rCBV maps in patients with proof of early and success- 
ful recanalization. 

Nuclear perfusion imaging of the brain using Tc99m- 
HMPAO SPECT also has been advocated for the man- 
agement of acute stroke, particularly in assisting clini- 
cal decision making for proper patient selection [5, 65- 
67]. Relative comparisons of the residual CBF can be 
made by calculating ratios of activity in normal and af- 
fected regions of the brain. Shimosegawa et al. [68] 
showed that these ratios could be used to estimate the 
infarction (viability) threshold in an untreated group of 
patients imaged within 6 hours of symptoms onset; the 
reported threshold was 0.48 (SD=0.14). In another 
study, reperfusion occurring within approximately 7 
hours after onset of symptoms significantly reduced the 
development of infarction (reversibility) with a R/CE 
ratio (the ratio of ischemic regional activity to cerebel- 
lar activity) between 0.55 and 0.75 [69]. Others found 
that so-called moderate ischemia with residual relative 
CBF ratios between 0.35 and 0.70 was suitable for in- 
tra-arterial thrombolysis [70]. Our data show that the 
pretreatment CBF judged by SPECT in patients with 
complete recanalization is significantly different among 
reversible ischemia, infarction, and hemorrhage (Fig. 
lb) [7]. The risk of hemorrhagic transformation in 
acute stroke, when treated within 5 hours with intra-ar- 
terial thrombolysis, primarily depended on residual 
CBF of ischemic tissue judged by pretreatment SPECT 
(35%). Within 5 hours of symptoms onset, the develop- 
ment of infarction or hemorrhage appeared to depend 
on both the residual CBF and on the duration of is- 
chemia (Fig. lb). However, beyond 5 hours from the on- 
set of symptoms, the residual CBF was the only para- 
meter that appeared to be predictive of treatment out- 
come. It must be stressed that our data also showed that 




24 



W.T.C. Yuh, T. Taoka, T. Ueda, M. Maeda 



relative reductions in rCBF during an acute stroke cor- 
related with the neurological outcome in the setting of 
acute therapeutic intervention, supporting the notion 
that such perfusion measurements can provide impor- 
tant information that could be used for optimizing pa- 
tient selection. This predictability included both overall 
neurological outcome and risk of hemorrhagic conver- 
sion for a wide spectrum of time intervals from symp- 
toms onset, including some cases that were well beyond 
the conventional 6-hour therapeutic window used for 
intra-arterial thrombolysis [7, 71]. 

Conclusions 

The role of acute stroke imaging is evolving from simple 
detection and delineation of ischemic injury to the more 
important issue of predicting therapeutic outcome. To 
achieve this goal, hemorrhage revealed with conventional 
diagnostic imaging and functional imaging in an untreated 
population of patients may not always be useful for assess- 
ing the true capabilities of various imaging modalities that 
can be used for predicting therapeutic outcome in acute 
stroke intervention. Most published studies focused on pa- 
tients and lesions that neither received treatment nor had 
demonstrable evidence of reperfusion. The effectiveness of 
pretreatment imaging or therapy cannot be adequately ad- 
dressed if a salvaging effort has not been attempted or 
failed. With the coexisting heterogeneity of disease state 
among patients or lesions, and the various imaging modal- 
ities available for assessing cerebral ischemia, the tradi- 
tional efforts to obtain absolute measurements of various 
predictive parameters may detract from the more important 
goal of finding prompt and practical assessments that can 
rapidly facilitate triage of the acute stroke patient consid- 
ered for therapeutic intervention. This need may favor use 
of somewhat more simplistic and semiquantitative method- 
ologies. Currently, cerebral perfusion imaging using either 
SPECT or MRI appears to be able to provide this type of 
prompt and predictive information since it is most closely 
tied to the primary underlying pathophysiology (i.e. hy- 
poperfusion). Therefore, we believe further efforts need to 
be made in applying these modalities prospectively for the 
purpose of improving treatment eligibility (extending ther- 
apeutic window) and effectiveness. 

Note: This chapter is based on: Imaging helps identify who bene- 
fits frome stroke intervention. 1999, Diagn Imaging 19:70-82. 



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Amazon, Seattle, pp 487-490 




IDKD 2004 



Brain Ischemia 

R. von Kummer 

Department of Neuroradiology, Universitatsklinikum Carl-Gustav-Carus, Dresden, Germany 



Introduction 

Acute focal cerebral ischemia, with brain perfusion be- 
low 20 ml/min per 100 g tissue, causes an immediate 
loss of function of the affected brain area and a cascade 
of pathologic events including tissue water uptake re- 
sulting in tissue necrosis if perfusion declines further. 
Patients with acute cerebral ischemia present with 
hemiparesis, hemianopia, speech disturbance, or im- 
pairment of consciousness. The differential diagnosis 
includes intracranial hemorrhage, congestive or hyper- 
tensive cerebral edema, focal encephalitis, demyelina- 
tion disorder, metabolic disturbance, or tumor. Brain 
imaging is absolutely necessary for an exact diagnosis 
and to assess the acute pathology of the brain. 
Information provided by computed tomography (CT) 
and magnetic resonance imaging (MRI) should guide 
the management of stroke patients and can thus finally 
influence clinical outcome if the applied treatment is 
effective. 

Imaging can be clinically efficacious on 5 different 
levels: (1) technical capacity; (2) diagnostic accuracy; (3) 
diagnostic impact; (4) therapeutic impact; and (5) patient 
outcome [1]. The technical advantage of CT and MRI in 
acute stroke is the capability to reproducibly display rec- 
ognizable images that demonstrate stroke pathology with 
good intra- and interobserver reliabilities [2]. This paper 
concentrates on the first level of clinical efficacy in 
stroke imaging, because there are few prospective data 
showing that imaging has a proved impact on treatment 
and outcome. 

CT and MRI are capable of detecting intracranial he- 
morrhage and other diseases that may mimic stroke, the 
pathology of major brain arteries, brain tissue hypoper- 
fusion, brain swelling, ischemic brain edema, and brain 
tissue necrosis. Not all information may be crucial to 
treat the patient properly. Currently, only reperfusion 
therapy with intravenous recombinant tissue plasmino- 
gen activator (rt-PA) or intra-arterial prourokinase 
within the first 6 hours of stroke onset has been shown 
to be effective [3-6]. The rationale for reperfusion ther- 
apy is a volume of ischemic brain tissue that has 



chances to regain function. Consequently, imaging 
should aim to differentiate the following pathological 
states: 

1. Intracranial hemorrhage and other pathologies that 
cause a stroke-like syndrome, because thrombolytic 
agents are ineffective or even risky in these dis- 
eases. 

2. Brain tissue at risk of hypoperfusion, i.e. tissue that 
cannot survive without enhancement of blood flow, 
but is still viable at the time of examination for an 
unknown period. Reperfusion therapy may be bene- 
ficial if a considerable volume of such tissue is pre- 
sent [7-8]. 

3. Irreversibly injured brain tissue, because this tissue 
cannot recover by definition, even if blood supply is 
restored immediately after diagnosis. Moreover, reper- 
fusion of damaged brain tissue may increase ischemic 
edema and the risk of severe hemorrhage [9]. 

Imaging of Intracranial Hemorrhage 

Computed Tomography 

After acute intracranial hemorrhage, blood appears on 
CT as a hyperattenuated, often space-occupying mass 
and is easily detected within cerebrospinal fluid (CSF) 
or brain parenchyma. The degree of hyperattenuation 
depends on the amount of blood, whether it is clotted 
or not, and whether the blood is intermixed with CSF 
or brain tissue. Consequently, the assessment of brain 
hemorrhage can be difficult if blood is only one com- 
ponent of the brain pathology. Sensitivity of CT for de- 
tection of parenchymal hemorrhage is considered to be 
as high, although it was not tested due to a lack of a 
gold standard. Small hemorrhages in the brain 
parenchyma or subarachnoid space can be missed. 
Emergency physicians had an error rate in stroke de- 
tection by CT twice that of neurologists and radiolo- 
gists, and only 17% of emergency physicians, 40% of 
neurologists and 52% of radiologists recognized all in- 
tracranial hemorrhages [10]. 




28 



R. von Kummer 



Acute hemorrhages usually present as hyperattenuat- 
ing clots without surrounding edema. If marked edema is 
present under these circumstances, underlying neoplasm 
or venous obstruction should be suspected. The location 
of the hematoma often provides clues about its underly- 
ing etiology. Multiple hemorrhagic lesions should make 
one think about metastatic disease, coagulopathy, or cere- 
bral amyloid angiopathy. 

In the subacute and chronic stages, cerebral bleedings 
become isodense on CT, whereas they display high and 
low signal intensity on MRI caused by methemoglobin 
and hemosiderin, which can be detected even years after 
bleeding [11]. 

Magnetic Resonance Imaging 

On MRI, an acute hemorrhage containing mainly oxy- 
hemoglobin is isointense on T1 -weighted images and 
hyperintense on T2-weighted images. Thus, it is easily 
missed if located within the CSF space or misinterpret- 
ed if located within brain parenchyma (Fig. 1). While 
MRI has traditionally been considered to be insensitive 
to hematomas in the clinical setting, it is now quite ob- 
vious that MRI can reliably detect acute cerebral hem- 
orrhages. Susceptibility-sensitive gradient echo tech- 
niques like T2*-weighted sequences demonstrate acute 
intracerebral hematomas with low signal intensity due 
to the susceptibility effect of deoxyhemoglobin. 
Linfante et al. [12] found that acute hematoma is com- 
posed of 3 distinct areas: (1) a center, which has an 
isointense or hyperintense heterogeneous signal on T2*- 
weighted and T2-weighted images; (2) a periphery that 



is hypointense (susceptibility effect) on susceptibility- 
weighted and T2-weighted images; and (3) a rim that is 
hypointense on T1 -weighted images and hyperintense 
on T2-weighted images, representing vasogenic edema 
encasing the hematoma [12]. 

MRI shows hemorrhage in its different stages, en- 
abling the assessment of bleeding onset, whereas CT is 
positive only for acute and subacute hemorrhages. In 
stroke patients, MRI may show cerebral deposits of he- 
mosiderin after clinically silent microbleeds, which 
may be a risk factor for major cerebral hemorrhages 
[13, 14]. Moreover, there are hints that MRI can detect 
acute cerebral bleedings earlier than CT. If this can be 
proved in larger studies, MRI will become the gold 
standard for assessing intracerebral hemorrhage and 
will be required before thrombolytic and antithrombot- 
ic therapies. 

Regarding the differential diagnosis between ischemic 
and nonischemic lesions like brain tumors, plaques of 
multiple sclerosis, encephalitis, metabolic disorders, and 
venous infarctions, MRI offers a variety of advantages 
over CT, like better tissue contrast and multiplanar imag- 
ing. Systematic studies comparing the technical capacity 
of both imaging modalities in this regard are however 
lacking. 

Imaging of Tissue at Risk 

Three possibilities exist to identify, using CT or MRI, 
brain tissue at risk of being irreversibly injured by hy- 
poperfusion: 




Fig. la-c. A 72-year-old man with sudden onset of memory disturbance, headache and disorientation one day before imaging, a 
T1 -weighted image shows an isointense mass in the right temporal lobe (arrows), b On T2-weighted image, this mass has hyper- 
and hypointense portions representing an acute hemorrhage with oxyhemoglobin (hyperintense, black arrows) and deoxyhemoglo- 
bin (hypointense, white arrows). The surrounding hyperintense rim (arrow heads) most probably represents edema, c CT scan ob- 
tained within 1 hour of the MR images. Interestingly, it shows hyperattenuation only in the somewhat older portions of the hemor- 
rhage with deoxyhemoglobin (arrows). The other portions of the hemorrhage are still isodense indicating that CT may be insensi- 
tive for acute hemorrhage 





Brain Ischemia 



29 



1 . Assessment of arterial occlusion with estimation of the 
territory supplied by this artery. 

2. Assessment of brain tissue swelling due to compen- 
satory arterial vasodilatation. 

3. Direct assessment of hypoperfused tissue volume. 
These approaches require additional information about 

the proportion of tissue that is already irreversibly in- 
jured. 

Arterial Occlusion 

The site of arterial occlusion can be detected with cross- 
sectional CT or MRI, CT or MR angiography, Doppler 
ultrasound, and digital subtraction angiography (DSA). 

CT and CT Angiography 

Thromboembolic occlusion of major brain arteries may 
present on unenhanced CT as a hyperattenuating arterial 
segment in comparison to other arterial segments. The 
interobserver agreement on such “hyperdense artery 
signs" varies between poor (k=0.20) and moderate 
(k=0.63) [15-17]. 

Computed tomographic angiography (CTA) requires 
spiral CT techniques and the bolus injection of a contrast 
agent [18]. Thus, patients with allergic reactions to io- 
dine or renal dysfunction usually cannot be studied with 
CTA. The CTA examination can be performed immedi- 
ately after an unenhanced CT scan. Preliminary data 
suggest that CTA is reliable in visualizing obstruction of 
major intracranial arteries and veins [18]. CTA is an ex- 



cellent technique to find out whether the obstruction of 
a major artery is the cause of stroke, to differentiate be- 
tween basilar artery and middle cerebral artery (MCA) 
occlusion, and to assess whether spontaneous recanal- 
ization has occurred. 

MRI and MR Angiography 

On spin echo sequences, the major brain-supplying arter- 
ies display low signal because of high blood flow veloc- 
ity (signal flow void). High signal or lack of flow void in- 
dicates arterial occlusion or low flow (Fig. 2a). In the 
case illustrated in Fig. 2, the territory of disturbed diffu- 
sion (Fig. 2b) does not match that of the distal MCA 
trunk occlusion. Moreover, the time-to-peak (TTP) para- 
meter image (Fig. 2c) shows increased flow with earlier 
appearance of the contrast peak within the left basal gan- 
glia. These findings are explained by an initial occlusion 
of the proximal MCA trunk and distal migration of the 
thrombus. 

Magnetic resonance angiography (MRA) using time- 
of-flight (TOF) or phase contrast (PC) sequences is a 
noninvasive test that can image larger extra- and in- 
tracranial arteries and veins. After a bolus injection of 
contrast medium, the brain-supplying arteries can be im- 
aged from the aortic arch up to the circle of Willis with- 
in 10 seconds. These contrast-enhanced images are inde- 
pendent of blood flow velocity and turbulence in contrast 
to TOF and PC techniques. They thus reflect arterial mor- 
phology and pathology more reliably than TOF and PC 
images. Contrast-enhanced MRA may be the method of 
choice if a quick overview over the extra- and intracranial 




Fig. 2a-c. A 37-year-old woman with MCA occlusion, a Proton density- weighted MR image shows a lack of flow void in the left distal 
middle cerebral artery trunk {arrow). The occlusion was confirmed by DSA. B Diffusion-weighted image (DWI) shows increased signal 
in the middle portion of the MCA territory and additionally within the left striatum, a territory supplied by the lenticulostriatal arteries that 
originates proximal to the occlusion site, c Time-to-peak (TTP) parameter image shows an area of delayed contrast peak exactly matching 
the high signal on DWI. Within the striatum, however, blood flow is accelerated. This mismatch can be explained by initial proximal MCA 
trunk occlusion, followed by a migration of the thrombus into the periphery. In fact, a hyperdense segment of the proximal MCA trunk 
was visible on the first CT scan obtained 30 minutes after the onset of symptoms 





30 



R. von Kummer 



arteries is wanted. Three-dimensional (3D) PC sequenees 
are useful in the diagnosis of venous occlusions. MRA 
can be performed immediately after brain tissue imaging. 
The results of TOP or PC MRA should be interpreted 
with caution because a high-grade stenosis is often over- 
estimated. 



Detection of Brain Tissue Swelling and 
Vasodilatation 

The enlargement of anatomical structures such as the 
cerebral cortex and the effacement of CSF spaces suggest 
brain tissue swelling and can be detected with CT and 
MRI. CT may detect brain tissue swelling without hy- 
poattenuation for a short period early after arterial ob- 
struction. Compensatory arterial dilatation due to low 
perfusion pressure or passive arterial dilatation due to 
high venous pressure cause this type of swelling [19, 20]. 
Six neuroradiologists agreed on tissue swelling in 45 CT 
images of acute stroke patients with a k of 0.56-0.59 [16]. 
Compensatory arterial dilatation is associated with a pro- 
longation of the mean transit time. Flow velocity affects 
the intraluminal signal on MRI so that contrast enhance- 
ment becomes visible in vessels with slow flow (Fig. 3a, 
b). Vascular enhancement is an MRI sign of compro- 
mised flow [21]. 

Perfusion Imaging 

Brain perfusion means the volume of blood that flows per 
minute through a certain amount of brain tissue, usually 
100 g. To quantify brain perfusion, clinicians use a con- 



trast agent such as an intra-arterial nondiffusible flow 
tracer. Both CT and MRI permit clinicians to follow the 
contrast agent’s concentration over time in each tissue 
voxel and to calculate the mean transit time (MTT), cere- 
bral blood volume (CBV), and cerebral blood flow (CBF) 
from the concentration curve. True quantification of per- 
fusion requires several conditions that can hardly be 
achieved [22, 23]. A robust method to image cerebral per- 
fusion without true quantification is the determination of 
the time from contrast medium entry to peak concentra- 
tion (“time-to-peak”, TTP). A parameter image then dis- 
plays areas of delayed concentration peaks on CT or 
MRI. This method is sensitive to detect differences be- 
tween gray and white matter (Fig. 3c). Perfusion imaging 
with CT is restricted to 1-4 sections, whereas MRI se- 
quences allow clinicians to image the entire brain. 
Because CBF often changes over time, it makes sense to 
repeat perfusion imaging. MRI has then the advantage of 
avoiding radiation injury. 



Imaging of Irreversibly Injured Brain Tissue 

Because of its high vulnerability, brain tissue may be al- 
ready irreversibly injured when the patient presents. 
Reperfusion treatment is ineffective when a relevant pro- 
portion of brain tissue is already dead. Moreover, severe- 
ly injured brain tissue is prone to malignant edema or 
clinically relevant bleeding during reperfusion. A reliable 
assessment of the amount of ischemic damage is, there- 
fore, regarded to be most important for stroke treatment. 

The early assessment of irreversibly injured brain tis- 
sue is not easy even with histological examination [24]. 




Fig. 3a-c. A 51 -year-old man with attacks of right-sided hemiparesis and remaining weakness of right hand, a, b T1 -weighted MR images 
after contrast medium injection of show (a) lack of flow void in the left carotid siphon (arrow) and (b) marked intra-arterial contrast en- 
hancement on the distal branches of the left middle cerebral artery indicating low flow and hemodynamic compromise (arrows), c Time- 
to-peak parameter image shows a delay of contrast medium peaks in the left middle cerebral artery territory 





Brain Ischemia 



31 



Cerebral blood flow (CBF) of 8-12 ml/min per 100 g is 
accepted to be the flow threshold for structural integrity 
[25]. A sudden decrease in cerebral perfusion below 8 
ml/min per 100 g causes the gray matter to immediately 
take up water [26-28]. The amount of water accumulating 
during ischemia was significantly correlates with the du- 
ration of ischemia [29]. Significant resolution of brain 
edema is possible only if ischemia has lasted less than 15 
minutes. This early type of ischemic edema occurs in tis- 
sue that was exposed to perfusion below the threshold for 
maintaining structural integrity. Imaging ischemic edema 
may be useful to identify the proportion of ischemic brain 
tissue that is irreversibly damaged [30]. 

Computed Tomography 

X-ray attenuation is linearly proportional to specific 
gravity and thus allows monitoring tissue water content 
[31]. An increase of tissue water content by 1% causes a 
decrease of X-ray attenuation by 2.6 HU in gels [32] and 
by 2.1 HU in experimental, cryogenically induced brain 
edema. Coregistration of CT attenuation and CBF re- 
vealed that hypoattenuation develops only in areas of crit- 
ically hypoperfused brain tissue [33]. The mean CBF in 
the affected MCA territory of patients with hypoattenu- 
ating basal ganglia (7 ml x min"^ 100 g'^) was signifi- 
cantly lower than that of patients who did not have these 
findings (17 ml x min"^ 100 g“^) [34]. A decline in cere- 
bral blood volume (CBV) may add to the decrease in X- 
ray attenuation. 

Using a CT window width of 80 HU, the minimal vis- 
ible contrast is at 3-4 HU, which corresponds to an in- 
crease in brain tissue water content of about 1.5%. This 
suggests that the first and potentially reversible stage of 
the developing ischemic edema cannot be seen on CT be- 
cause the decline of attenuation has not reached the con- 
trast resolution of 4 HU. In other words, a normal CT ex- 
amination in a patient with stroke excludes hemorrhage 
and other disease, but cannot exclude ischemic edema in 
an early stage. This insensitivity of CT for the first stage 
of ischemic edema has, however, a clear advantage by the 
increased specificity of the finding: CT depicts ischemic 
edema only at its irreversible stage. Hypoattenuating 
brain parenchyma on CT after arterial occlusion indicates 
severe ischemia under the critical level of structural in- 
tegrity for 1-3 hours. Under clinical conditions, hypoat- 
tenuation may appear already 22 minutes after the onset 
of symptoms [30]. It is not yet known, however, whether 
hypoattenuation of ischemic brain tissue can disappear if 
the tissue is reperfused within less than 30-60 minutes 
and to what extent changes in CBV contribute to changes 
in CT attenuation. 

Because of its subtlety, early ischemic edema (Fig. 4) 
is recognized with only moderate interobserver reliabili- 
ty [16, 17, 35]. The National Institute of Neurological 
Disorders and Stroke rt-PA Stroke Trialists and others 
demonstrated that training in CT reading considerably af- 
fects the sensitivity of detecting ischemic edema [35, 36]. 




Fig. 4a, b. Patient with severe right-sided hemiparesis. a The ear- 
ly CT image (1 hour after onset of symptoms) shows subtle hy- 
poattenuation of the left insular, frontal, and temporal cortices (ar- 
rows). b Twenty-four hours later, this area became clearly hypo- 
dense, shows a space-occupying effect, and contains a small 
hematoma 



Attempts were made to improve the capability of CT in 
detecting ischemic edema by performing a density-dif- 
ference analysis between both cerebral hemispheres, by 
varying window width and center level, and by using a 
quantitative score [37-39]. 

Magnetic Resonance Imaging 

MRI has more than one possibility to image ischemic 
brain tissue changes. It is generally accepted that signal 
changes that appear relatively late after focal ischemia 
represent irreversible damage. The increase in signal on 
T2-weighted spin echo sequences and the corresponding 
decrease on T1 -weighted sequences mainly represent tis- 
sue water uptake and may indicate ischemic edema or, 
later, ischemic necrosis. These signal changes appear 
hours after stroke onset and are, therefore, irrelevant for 
acute stroke treatment. However, MR images that have 
been specifically sensitized to the translational diffusion 
of water (diffusion- weighted images, DWI) can reveal tis- 
sue contrast based on properties essentially very different 
from those exploited by standard sequences [40, 41]. In 
ischemic brain areas with CBF values of 30 ml/min per 
100 g and less, the extracellular fluid compartment is re- 




32 



R. von Kummer 



duced because of a shift of water from the extracellular 
space into the cells [27]. At the same ischemic threshold, 
proton diffusion becomes impaired [42, 43]. 

Within 15-30 minutes after onset of focal ischemia be- 
low that threshold, the apparent diffusion coefficient 
(ADC) decreases by 30%-50%, while Tl- and T2-weight- 
ed MR images remain normal [40]. This time course is 
consistent with the complete loss of tissue adenosine 
triphosphate, loss of sodium and potassium membrane 
pump activities, and consequent cellular edema in se- 
verely ischemic brain tissue [44]. Increased signal on 
DWI precisely indicates the areas with ATP depletion. 
Induction of cellular edema by means other than focal is- 
chemia also reduces ADC [45]. 

It is clear from these observations in experimental ani- 
mals that DWI is highly sensitive in detecting brain areas 
with ATP depletion and consequently high risk for irre- 
versible injury. Moreover, its negative predictive value for 
ischemic damage must be high. In stroke patients, brain 
tissue with high signal on DWI or with low ADC is either 
going to die or may recover with reperfusion [46-48]. 

Conclusions 

The differentiation of the stroke syndrome and the as- 
sessment of acute brain pathology are the main condi- 
tions for a carefully directed and successful treatment. 
CT and MRI have the technical capacity to reproducibly 
display recognizable images that demonstrate pathology 
of acute stroke, brain-supplying vessels, and diseases that 
mimic stroke. MRI is superior to CT in detecting acute 
and chronic states of brain hemorrhage. DWI is highly 
sensitive in detecting ischemic brain regions with deple- 
tion of ATP and high risk of irreversible tissue damage. 
If DWI is negative in an acute stroke patient or shows on- 
ly small areas of disturbed diffusion, the patient has a 
good prognosis if cerebral blood flow is quickly restored. 
Hypoattenuating brain tissue on CT is difficult to recog- 
nize in the very early stage of ischemic brain edema, but 
is a highly specific finding representing irreversibly in- 
jury. If a volume of hypoattenuating brain tissue is de- 
tected, the extent of damaged tissue determines the pa- 
tient’s prognosis and response to treatment. 

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IDKD 2004 



Haemorrhagic Cerebral Vascular Disease 

J. Byrne 

Department of Neuroradiology, Radcliffe Infirmary, University of Oxford, Oxford, UK 



Introduction 

This paper outlines a logical strategy for managing the 
imaging investigation of patients presenting with sponta- 
neous intracranial haemorrhage. Details of the patient’s 
acute and past medical histories may point to the cause of 
intracranial bleeding but in most instances it is imaging 
that distinguishes the victims of haemorrhagic from those 
with ischemic stroke. This crucial distinction triggers 
completely different diagnostic and therapeutic manage- 
ment paths. 

In the following paragraphs, I describe my protocols 
for identifying underlying structural lesions that require 



interventions to prevent rebleeding or progression. These 
lesions are most commonly vascular and, in some cir- 
cumstances, emergency interventions may be life-saving. 
It is therefore important for investigations to be appro- 
priate and timely. 

How Should the Patient with Haemorrhagic 
Stroke be Investigated? 

The first step is to triage patients (Fig. 1) into those like- 
ly to have an underlying structural lesion carrying a risk 
of rebleeding, those likely to have a ‘non-structural’ cause 



CT 



SAM 

±JVH 



Angiogiap^ 

CTA 

or 



ICH 



Parent < 40 y»rs|4 



Anourysm 
Of AVM? 



I Yes !! 

T 

loSAtEVJ 



No i 

— ^ Of 



OSA 



H 



STOP 



Penmesencephal^o 

dt:£'tnbution7 



HiaJtory of 
r| bp or bleeding 
diathesis? 



I M RA 



Aneurysm 




or AVM? 


AVMs"? 

j 


j Yes { j No 1 




♦ 


Yes ^ 



OSA I 



iCsrdnoma?' 




' Subdgfar , 

Bleedmg 

Dislhssis? 



Ves 

STOP 



T 




1'. .tfeC' 


. . 

1 MRI 
1 + 


j STOP 1 





No 

_ T _ 

MRI 




• 




Ves I 


1 No 


Yes 1 


j No ^ 




. .1 


? 




Considef 


STOP 


i STOP i 




biopsy 





Fig. 1. Flow diagram showing 
CT based diagnostic triage 
routes for patients with sponta- 
neous intracranial haemorrhage 





Haemorrhagic Cerebral Vascular Disease 



35 



that requires urgent diagnosis and treatment, and those 
unlikely to have an underlying lesion and therefore not 
requiring urgent interventions. 

Causes of Subarachnoid Haemorrhage 

Common causes of subarachnoid haemorrhage are: 

- Saccular aneurysm 

- Arterial dissection 

- Angiogram-negative perimeseneephalie haemorrhage 
Rarer causes are: 

- Brain or spinal arteriovenous malformations (AVMs) 
or arteriovenous fistulae (AVFs) 

- Dural AVFs 

- Pitituary apoplexy 

- Infectious aneurysms 

- Drug abuse (e.g. eoeaine) 

- Sickle eell disease (in children) 

- Bleeding diathesis (e.g. exeessive antieoagulation) 

Causes of Spontaneous Intracranial 
Haemorrhage 

Common causes of spontaneous intracranial haemor- 
rhage in the basal ganglia and thalamus are: 

- AVMs, ineluding eavernous malformations and eryp- 
tie AVMs 

- Lipohyalinosis 

- Moyamoya syndrome 

- Tumour 

- Bleeding diathesis 

In the lobar region, causes are: 

- AVMs, ineluding eavernous malformations and eryp- 
tie AVMs 

- Saeeular aneurysms 

- Venous thrombosis 

- Amyloid angiopathy 

- Tumour 

- Amphetamine and eoeaine abuse 



- Infeetious endoearditis 

- Bleeding diathesis 

Finally, in the cerebellum and brain stem, causes are: 

- AVMs, ineluding eavernous malformations and eryp- 
tie AVMs 

- Lipohyalinosis 

- Tumour 

- Amyloid angiopathy 

- Bleeding diathesis 

Causes of Spontaneous Subdural Haemorrhage 

Typieal eauses of spontaneous subdural haemorrhage are: 

- Saeeular aneurysm 

- Rupture of small pial vessels 

- Moyamoya syndrome 

- Dural AVFs 

- Dural metastases 

- Coagulation defeets 

Conclusions 

This presentation diseusses the role of eomputed tomog- 
raphy (CT), magnetic resonance imaging (MRI), and 
digital subtraetion angiography (DSA) in the diagnosis 
of these pathologies, with illustrative examples. The cru- 
eial role of CT as the primary imaging tool is empha- 
sised and the student will be taught to distinguish pre- 
dominantly lobar, subarachnoid, intraventricular and 
subdural locations of haemorrhage. Students will be 
taught features of the evolving eerebral haemorrhage 
over time and the resulting effeet on the imaging ap- 
pearanees of haematomas. 

Suggested Reading 

Davis S, Fisher M, Warach S (eds) (2003) Magnetic resonance 
imaging in stroke. Cambridge University, Cambridge 
Warlow CP et al (eds) (1996) Stroke: a practical guide to manage- 
ment. Blackwell Science, Oxford 




IDKD 2004 



Hemorrhagic Vascular Pathology 

M. Forsting, I. Wanke 

Department of Radiology and Neuroradiology, Institute of Diagnostic and Interventional Radiology, University of Essen, Essen, Germany 



Imaging Intracranial Hemorrhage 

Intracranial hemorrhage (ICH) is a frequent indication 
for emergent neuroimaging. To understand the appear- 
ance of clots on computed tomography (CT) and mag- 
netic resonance imaging (MRI), it is mandatory to know 
some details of clot formation. 

Initially, an intracerebral hematoma is composed of 
95%-98% oxygen-saturated hemoglobin, mainly contain- 
ing erythrocytes. Over the first 4-6 hours, the protein clot 
retracts, still containing intact biconcave red blood cells 
(RBCs) with oxygenated hemoglobin. During the next 48 
hours, the RBCs shrink and hemoglobin desaturates. 
During this period, the hematoma contains predominant- 
ly deoxygenated intracellular hemoglobin (remember, the 
RBCs are still intact). In the early subacute phase (a few 
days after the initial hemorrhage), oxidative denaturation 
of the hemoglobin progresses and deoxyhemoglobin is 
gradually converted to methemoglobin (MetHb). These 
changes first occur around the periphery of the 
hematoma and then progress centrally. RBCs continuous- 
ly lyse and release MetHb into the extracellular space. 
Afterwards, the hematoma starts to shrink to finally form 
a slit-like cavity containing a fluid similar to cere- 
brospinal fluid (CSF) and, as a long-standing marker of 
bleeding, ferritin- and hemosiderin-laden macrophages. 

Computed Tomography 

Fresh intracerebral blood typically appears hyperdense on 
CT due to the high protein concentration and high mass 
density. However, acute intracerebral hematoma occa- 
sionally appears isodense or even hypodense on CT. This 
occurs with extreme anemia, i.e. when the hemoglobin 
concentration drops to 8 g/dl. Another reason for prima- 
ry isodense clots on CT is a coagulation disorder. Failure 
of clot retraction results in a relatively isodense, acute 
ICH. 

Within 1-6 weeks, hemorrhage becomes virtually iso- 
dense with adjacent brain. Due the breakdown of the 
blood-brain barrier, hemorrhage can mimic an abscess on 
contrast-enhanced studies. 



Magnetic Resonance Imaging 

MRI of intracerebral hemorrhage is complex and requires 
much knowledge on the pathophysiology of blood degra- 
dation. The signal is mainly influenced by the oxidation 
state of hemoglobin (Hb) and by the protein concentra- 
tion. Extrinsic factors are the pulse sequences and the 
field strength of the MRI system. Generally speaking, de- 
oxy-Hb appears isointense with brain on T1 -weighted im- 
ages and hypointense on T2-weighted images; extracellu- 
lar MetHb (subacute clots) appears bright on Tl- and T2- 
weighted images; and hemosiderin (chronic state) is dark 
on Tl- and T2-weighted images. However, this is only a 
rough summary. We strongly recommend further study of 
hemoglobin degradation and its relationship to the MRI 
signal. This allows one to recognize intratumoral hemor- 
rhages because the oxygen content within a tumor is low- 
er and, therefore, the time course of signal changes is de- 
layed. 

Hemorrhagic Diseases 

The three most common hemorrhagic diseases are hyper- 
tension, aneurysms and vascular malformations. 
Hypertensive hemorrhage is the most common cause of 
intracranial hemorrhage and has a predilection for areas 
supplied by penetrating branches of the middle cerebral 
and basilar arteries. Two thirds of these bleedings are lo- 
cated in the basal ganglia; in 50% of these, there is also 
associated intraventricular hemorrhage. Other relatively 
common sites of hypertensive ICH are the cerebellum 
and pons. In addition to the location of the bleeding, find- 
ings of lacunar stroke or white matter disease may further 
enhance the suspicion of a hypertensive cause. 

Patients usually undergo CT first. If in doubt about the 
hypertensive character of the hematoma, MRI is a second 
step. Finally, the majority of these patients needs angiog- 
raphy, especially if younger than 70 years and with bleed- 
ing in a so-called atypical location. 

If the hemorrhage is not hypertensive (i.e. the patient 
has no specific history and the hematoma is atypically lo- 
cated), a vascular malformation or an intracranial 




Hemorrhagic Vascular Pathology 



37 



aneurysm is the most likely cause of ICH. The purpose of 
this summary is not to fully eover the large field of these 
diseases, but to give a short overview of pathology, elin- 
ical presentation, imaging findings and treatment op- 
tions. The seminar itself provides numerous illustrations 
to enhance knowledge in this field. 

Intracranial Aneurysms 

Usually, intracranial aneurysms are divided into three ba- 
sie types: saceular, fusiform and dissecting. They can 
arise as solitary (70%-75%) or multiple (25%-30%) vas- 
cular lesions, usually located at the circle of Willis. The 
vast majority of aneurysms (85%) are located in the an- 
terior circulation and only 15% are in the posterior eircu- 
lation. Most saccular aneurysms are not considered to be 
congenital, but develop during life. The most common lo- 
cation (30%-35%) is the anterior communicating artery. 
However, many of these so-called AcomA aneurysms do 
have their origin at the A1-A2 junction of the anterior 
cerebral artery and do not involve the anterior communi- 
cating artery. Internal carotid and posterior communicat- 
ing artery aneurysms account for 30% and middle cere- 
bral artery (MCA) bifurcational aneurysms account for 
20%. Approximately 10% of intracranial aneurysms arise 
at the vertebrobasilar circulation: half develops at the 
basilar tip (with various levels of involvement of the PI 
segments) and the other half is from other posterior fos- 
sa vessels. Extremely rare are aneurysms of the anterior 
inferior cerebellar artery (AICA) and of the vertebral 
artery (VA) without involvement of the VA-PICA junc- 
tion or the vertebrobasilar union. 

Most intracranial aneurysms remain undetected until 
the time of rupture. Subarachnoid hemorrhage (SAH), a 
medical emergency, is by far the most common initial 
clinical presentation. A history of abrupt onset of a severe 
headache of atypical quality (“the worst headache in my 
life”) is typical of SAH. Headache onset may or may not 
be associated with brief loss of consciousness, nausea 
and vomiting, focal neurologic deficits, or meningism. 
Despite the characteristic history, SAH is frequently mis- 
diagnosed. Nearly half of patients presents with milder 
symptoms caused by a warning leak before full rupture 
of the aneurysm. 

Although the pathogenesis and etiology of cerebral 
aneurysms have been studied extensively, both are still 
poorly understood. Endogenous factors such as elevated 
blood pressure, the special anatomy of the circle of 
Willis or the effect of hemodynamic factors, particular- 
ly originating at vessel bifurcations, are all known to be 
involved in the growth and rupture of an aneurysm. 
Arteriosclerosis and inflammatory reactions, however, 
may also have an impact. Exogenous factors such as cig- 
arette smoking, heavy alcohol consumption and certain 
medications are thought to be risk factors in the patho- 
genesis of aneurysm or to at least increase the risk of 
rupture. 



Furthermore, a genetic component is discussed. First- 
degree relatives of patients with an aneurysmal SAH have 
a significantly higher risk of harboring a cerebral 
aneurysm compared to the normal population. 

The annual incidence of SAH in the Western world is 
around 6-10 per 100 000 persons, peaking in the sixth 
decade, with risk for SAH increasing linearly with age. 
The annual incidence in other countries like Finland or 
Japan is higher - about 15 per 100 000 persons. SAH ac- 
counts for one-quarter of cerebrovascular deaths. 
Aneurysms increase in frequency with age beyond the 
third decade, are approximately 1.6-times more common 
in women, and are associated with a number of genetic 
conditions. 

Hydrocephalus, rebleeding from aneurysmal rerup- 
ture, and cerebral vasospasm with ischemia are the three 
major complications following SAH. Intracerebral 
hematoma occurs in up to 30% of patients with aneurys- 
mal rupture. The outcome is clearly worse than with 
SAH alone. If a space-occupying hematoma compress- 
ing neural structures is present, immediate evacuation 
of the hematoma is mandatory, eventually in combina- 
tion with clipping of the aneurysm, if it can be identi- 
fied. In this setting, CT angiography is a valuable and 
fast imaging modality to disclose the aneurysm prior to 
surgical intervention. Immediate surgical evacuation is 
also indicated in acute subdural hematoma, which is 
usually associated with recurrent aneurysmal rupture. 
However, this can also occur with the initial SAH or can 
be the only extravascular space involved after aneurys- 
mal rupture. 

Vasospasm is a major cause of morbidity and mortali- 
ty in patients after SAH and is often associated with de- 
layed cerebral ischemia. However, many patients are 
asymptomatic despite various degrees of angiographical- 
ly visible vasospasm. Although vasospasm is noted an- 
giographically after SAH in 70% of cases, it becomes 
symptomatic only in about one-half of these patients. 

If SAH is suspected clinically, CT of the brain is the 
initial diagnostic imaging modality of choice and clearly 
the gold standard to identify, localize and quantify sub- 
arachnoid hemorrhage. Typically, the subarachnoid blood 
appears hyperdense on an unenhanced CT image. The 
pattern of SAH can suggest the location of the underly- 
ing aneurysm. Intraparenchymal hemorrhage occurs with 
aneurysms of the posterior communicating artery and 
middle cerebral artery more frequently than with other 
locations. Interhemispheric or intraventricular hemor- 
rhage, occurring in about 50% of patients in autopsy 
studies, is characteristic of anterior communicating artery 
or distal anterior cerebral artery aneurysms. Ruptured 
posterior inferior cerebellar artery (PICA) aneurysms al- 
most always coexist with hydrocephalus and intraventric- 
ular hemorrhage in the fourth ventricle, which can also 
be seen on CT. Intracerebral hemorrhage is also more 
common in patients who rebleed, since the first bleeding 
may lead to fibrosis of the surrounding subarachnoid 
space and adhesion of the aneurysm to the brain. 




38 



M. Forsting, I. Wanke 



Subdural hematoma occurs in about 5% of patients, but 
is rarely the only location of bleeding. 

Small amounts of SAH may be overlooked, thus CT 
images should be carefully read. However, even if the CT 
scan is really normal (no reading fault), aneurysmal SAH 
cannot be ruled out. The sensitivity of CT for detecting 
SAH depends on the volume of the extravasated blood, 
the hematocrit, and the time elapsed after the acute event. 
Using modern scanners and performing the analysis 
within 24 hours after ictus, CT detects SAH in up to 95% 
of cases. However, due to dilution by CSF, the density of 
the hematoma decreases rapidly over time; thus after on- 
ly a few days it may be impossible to demonstrate sub- 
arachnoid blood on CT. Sensitivity of CT thus decreases 
to 80% at day 3, 70% at day 5, 50% at one week, and 
30% at 2 weeks. 

However, if CT is negative despite a convincing histo- 
ry of sudden headache, lumbar puncture is still the next 
diagnostic step to rule out SAH, if there is no contraindi- 
cation such as a bleeding disorder or space-occupying in- 
tracranial lesion. Lumbar puncture should not be per- 
formed before 6 hours after onset of headache; preferably 
12 hours should elapse between onset of headache and 
spinal tap. After this interval, sufficient lysis of erythro- 
cytes has occurred to form bilirubin and oxyhemoglobin. 
These pigments give the CSF the “typical” xanthochrome 
yellowish tinge after centrifugation, an essential feature 
in the differentiation from traumatic SAH. This xan- 
thochromia is invariably detectable for at least 2 weeks, 
usually 3 (in 70% of patients) to 7 weeks after SAH. 

Identification of factors predictive of outcome or spe- 
cific complications is important in the management of 
SAH. The risk of a given patient to suffer from va- 
sospasm can be estimated by the location, thickness, and 
density of subarachnoid blood on CT. In 1980, Fisher and 
colleagues described 47 patients in whom the amount and 
distribution of subarachnoid blood after aneurysmal rup- 
ture on the initial CT correlated with the subsequent oc- 
currence of vasospasm demonstrated by angiography. 
Two (1 1%) of 18 patients developed vasospasm when no 
or diffuse thin SAH was present on CT, whereas none did 
with only intraventricular or intracerebral hemorrhage. 
Of 24 patients with diffuse, thick SAH, 23 (96%) devel- 
oped severe symptomatic vasospasm. Since then, the CT- 
based Fisher classification (Table 1) of quantifying local 
amounts of subarachnoid blood as a powerful predictor 
for the occurrence of vasospasm and delayed cerebral is- 



Table 1. Fisher’s grading scale for subarachnoid hemorrhage (SAH) 



Group 


Subarachnoid blood 


Risk of vasospasm 


1 


No blood 


Low 


2 


Diffuse or vertical layers <1 mm 


Only moderate 


3 


Localized clot or vertical layer 




>1 mm 


High 


4 


Intracerebral or intraventricular 
clot with only diffuse or no SAH 





chemia has been confirmed by several clinical and ex- 
perimental studies. However, the predictive value of the 
Fisher grading system is not perfect. Never be too sure 
that a patient with a low Fisher score will not develop va- 
sospasm. All patients with SAH have to be carefully 
monitored during the first two weeks after ictus, regard- 
less of the initial Fisher score. 

Sensitivity of single-slice CT angiography (CTA) in 
the investigation of intracranial aneurysms has been re- 
ported to range from 67% to 100%, with an accuracy of 
approximately 90% and an interobserver agreement rang- 
ing from 75% to 84%. Nevertheless, this technique has 
limited sensitivity for aneurysms smaller than 3 mm 
(25%-64% compared with 92%-100% for aneurysms >3 
mm). Moreover, CTA has pitfalls if the aneurysm is lo- 
cated in a site where adjacent bone or considerable ves- 
sel overlap exist, such as the paraclinoid and terminal 
segments of the internal carotid artery (ICA) or at the 
MCA bifurcation. 

The implementation of multidetector row technology 
led to a major step forward in the field of CTA, notably 
for small vessels and intracranial aneurysms. This tech- 
nique reduces acquisition time despite the use of pitch 
values inferior to unity. Improvements in image quality 
and spatial resolution give better diagnostic results for 
intracranial aneurysms. Multirow CT technology will 
clearly facilitate work in emergency departments. 
Patients with a never-experienced-before headache and 
a negative unenhanced CT scan will get a quick and re- 
liable CTA examination. To optimize treatment planning 
and work-flow, CTA may also be used to stratify pa- 
tients into endovascular and surgical treatment groups. 
However, whether CTA really will allow us to decide 
which therapeutic modality is best still has to be deter- 
mined. In our opinion, there are drawbacks when de- 
scribing the anatomy of the neck and the true relation- 
ship of tiny vessels originating near the entrance of the 
aneurysm or adjacent to the aneurysmal dome. 
However, CTA clearly plays a role in the pretherapeutic 
phase in large or giant aneurysms. In these patients, it is 
often more difficult to visualize the exact anatomy of 
the neck and the relationship to adjacent bony struc- 
tures, such as in the paraophthalmic region, than with 
conventional digital subtraction angiography (DSA) 
alone. Moreover, CTA is helpful in the pretherapeutic 
planning of partially calcified and thrombosed 
aneurysms, and may help to determine the best treat- 
ment modality. In patients with large, space-occupying 
hematomas, CTA is clearly enough to rule out an un- 
derlying aneurysm. In this specific situation, DSA is 
probably no longer indicated. 

MRI and MR angiography (MRA) are increasingly 
used in the diagnostic work-up of patients with cerebral 
aneurysms. However, MRI is less suitable than CT in pa- 
tients with acute SAH because they are often restless and 
need extensive monitoring. MRI is used in patients with 
a negative angiogram to detect other causes of SAH, such 
as a thrombosed aneurysm or spinal vascular malforma- 




Hemorrhagic Vascular Pathology 



39 



tion, and it will increasingly be used in screening pro- 
grams and as a follow-up tool after endovascular therapy. 

Conventional MRI sequences are less sensitive than 
CT to SAH. Since SAH is mostly arterial in origin, the 
predominant form of hemoglobin is oxy-Hb. Immediately 
after the extravasation of blood into the subarachnoid 
space, there is a shortening in T1 due to the increase in 
hydration layer water owing to the higher protein content 
of CSF. This results in an increased signal on T1 -weight- 
ed and proton-density images. Fluid-attenuation inver- 
sion recovery (FLAIR) sequences are highly sensitive. 
The signal from CSF is almost completely reduced while 
producing a heavy T2-weighting. On FLAIR images, 
SAH appears hyperintense compared to CSF and the sur- 
rounding brain. Currently, it is widely accepted that even 
subtle amounts of subarachnoid blood can be detected by 
MRI when using FLAIR or proton-density weighted se- 
quences. False-positive FLAIR results may be caused by 
flow-related enhancement within the CSF. Even hypera- 
cute SAH can be detected with MRI. Compared with 
CSF, hyperacute blood has slightly lower signal intensity 
on T2*-weighted gradient echo images and increased sig- 
nal intensity on T2-weighted spin echo images. 
Aneurysm size is a crucial factor for the sensitivity. MRA 
studies consistently indicate sensitivity rates of more than 
95% for aneurysms larger than 6 mm, but much less for 
smaller aneurysms. For aneurysms smaller than 5 mm, 
which constitute as many as one-third of aneurysms in 
asymptomatic patients, detection rates of 56% and less 
have been reported. However, these aneurysms should 
not be ignored even if their rupture risk is low. In our ex- 
perience, in most patients, MRA can detect aneurysms as 
small as 3 mm; the problem to detect lesions below this 
size is well known. This should be taken into account for 
all screening programs, but also for those follow-up ex- 
aminations (after coiling) when the initial size of the 
aneurysm was around 3 mm. 

Present indications for MR angiography in the evalua- 
tion of cerebral aneurysms include: 

- Incidental findings on CT or MRI suspicious for an 
aneurysm 

- Evaluation of specific clinical symptoms (e.g. third 
cranial nerve palsy) or non-specific symptoms in pa- 
tients in whom an aneurysm may explain the clinical 
presentation (e.g. those with thunderclap-headache). 

- Contraindications for conventional angiography 

- Noninvasive follow-up of patients with known 
aneurysms or endovascularly treated aneurysms 

- Screening in high risk patients (e.g. first-degree rela- 
tives of patients with SAH or multiple aneurysms, pa- 
tients with polycystic kidney disease or with connec- 
tive tissue disease) 

Owing to its excellent spatial resolution, conventional 
cerebral angiography is still the gold standard for the de- 
tection of a cerebral aneurysm. Currently, this is per- 
formed during the first available moment after presenta- 
tion of the patient in hospital. Considering that the risk of 
hemorrhage is highest in the first 24 hours (4%), an ear- 



ly angiogram is crucial for any therapeutic decision and 
for the patient’s outcome. 

Cerebral angiography can localize the lesion, reveal its 
shape and geometry, determine the presence of multiple 
aneurysms, define the vascular anatomy and collateral 
situation, and assess the presence and degree of va- 
sospasm. Due to the frequency of multiple aneurysms, a 
complete four-vessel angiography examination is essen- 
tial. However, in case of a space-occupying hematoma, 
angiography of the most likely affected vessel is suffi- 
cient. Anteroposterior, lateral, and oblique views are sys- 
tematically performed with cross-compression to demon- 
strate the anterior communicating artery, if necessary. 
Additional views may be necessary to optimize demon- 
stration of the aneurysmal neck. If no aneurysm is found, 
selective catheterization of both external carotid arteries 
is performed to exclude a dural arteriovenous fistula. The 
potential for collateral circulation from the vertebrobasi- 
lar system may be evaluated when the vertebral artery is 
injected during carotid artery compression (Allcock’s 
test), demonstrating the patency, size and collateral po- 
tential of the PI segment of the posterior cerebral artery 
(PCA) and the posterior communicating artery ipsilater- 
al to the compressed carotid artery. 

As a prerequisite to angiography, survey of renal func- 
tion and coagulation factors is required in all patients. 
DSA is necessary; biplanar angiography facilitates the di- 
agnostic work-up and is useful for safe and fast thera- 
peutic interventions. It shortens examination time and in- 
creases the safety during aneurysm obliteration. High- 
quality fluoroscopy and roadmapping are essential to per- 
form intracranial interventions. 

The primary treatment goal of cerebral aneurysms is 
prevention of rupture. Surgical clipping has been the 
treatment modality of choice for both ruptured and un- 
ruptured cerebral aneurysms for decades. Twenty years 
ago, endovascular treatment was mainly restricted to 
those patients with aneurysms unsuitable for clipping due 
to the size or location, or in whom surgical clipping was 
contraindicated because of the general medical condition. 
Since the introduction of controlled detachable coils for 
packing of aneurysms, endovascular embolization is in- 
creasingly used. Numerous observational studies have 
published complications rates, occlusion rates and short- 
term follow-up results. These have been summarized up 
to March 1997 in a systematic review of 48 eligible stud- 
ies of 1383 patients with ruptured and unruptured 
aneurysms. Permanent procedural complications oc- 
curred in 3.7% of 1256 patients. More than 90% occlu- 
sion of the aneurysm was achieved in around 90% of pa- 
tients. The most frequent procedural complication was 
cerebral ischemia and the second most frequent compli- 
cation was aneurysm perforation, which occurred in 
about 2% of patients. Rerupture of angiographically suc- 
cessful coiled aneurysms may occur; long-term rates of 
rebleeding after endovascular coiling still need to be es- 
tablished. In 2002, the results of the International 
Subarachnoid Aneurysm Trial (ISAT) were published; the 




40 



M. Forsting, I. Wanke 



clear benefits of endovascular coiling will definitely 
change treatment strategies for patients with intracranial 
aneurysms. The endovascular approach will become the 
first-line treatment option, wherever it is available. New 
devices like selfexpandable stents for intracranial use 
now allow surgeons to treat even broad-based aneurysms. 
As a rule of thumb, around 70%-80% of intracranial 
aneurysms can nowadays be treated via the endovascular 
approach. 

Cavernomas 

Cavernomas, also called cerebral cavernous malforma- 
tions or cavernous angiomas, are characterized by en- 
dothelium-lined, sinusoidal blood cavities without other 
features of normal blood vessels like muscular and ad- 
ventitial layers. No brain tissue is present between the 
blood cavities, which are embedded in connective tissue. 
This is, from a pathological viewpoint, the major differ- 
ence between cavernoma and capillary telangiectasia. In 
the latter, there is intervening brain parenchyma between 
the vascular channels. During follow-up, growth of cav- 
ernomas can occur, but this is exclusively related to os- 
motic changes or differences (like in chronic subdural 
hematoma) and never related to infiltration or any active 
growth. The sinusoidal walls may be locally thickened or 
hyalinized with spots of calcification. Cavernomas may 
occur sporadically or after radiation therapy, and may al- 
so be hereditary following an autosomal dominant trait. 

No reliable study gives exact rates of incidence and 
prevalence of cavernomas, but some data are available. 
The prevalence, estimated on the basis of autopsy and 
MRI studies, is 0.5%-0.7%. The incidence has been esti- 
mated to be 0.4%-0.9%. Cavernomas account for 8%- 
15% of all intracranial vascular malformations. During 
the last two decades, incidence data have been confirmed 
by MRI-based retrospective studies. There is no gender 
preponderance, and up to 25% of all cavernomas are 
found in the pediatric population. Multiple cavernomas 
occur in up to 90% of familial cases and in around 25% 
of sporadic cases. Therefore, whenever you see a single 
cavernoma on the MR scan of a patient, make sure that 
this is the only one. 

Patients with cavernomas present with a variety of 
symptoms. Seizures are the most common symptom, ac- 
counting for 38%-55% of complaints. Other symptoms 
include focal neurologic deficits in 12%-45% of patients, 
recurrent hemorrhage in 4%-32%, and chronic headaches 
in 5%-52%. Brain stem cavernomas nearly never cause 
seizures. Most of these patients have typical brain stem 
symptoms such as diplopia, face or body sensory distur- 
bances, and ataxia. Without imaging, it is difficult to dis- 
tinguish on clinical grounds alone this subgroup of pa- 
tients with intratentorial cavernomas from those with 
multiple sclerosis. 

The majority of patients becomes symptomatic be- 
tween the third and fifth decades, and there is no definite 



association between symptoms and gender. The frequen- 
cy of asymptomatic cavernomas is not precisely known, 
but according to the literature, it seems to be around 40%. 

The central clinical problem in patients with caver- 
nomas is the question of hemorrhage. On a first view, this 
should be a simple question with a simple answer. 
However, both are wrong. The problem starts with the de- 
finition of hemorrhage and ends with rather individual 
answers for individual patients. 

On one side, hemorrhage can be defined clinically: 
first or sudden onset of new neurologic symptoms in a 
patient with a cavernoma is usually related to a new or 
first hemorrhagic event. However, the literature contains 
an amazing number of definitions and terms to describe 
cavernoma-related hemorrhage: overt hemorrhage, 
symptomatic hemorrhage, gross hemorrhage, microhem- 
orrhage, intralesional or perilesional ooze or diapedesis, 
clinically significant hemorrhage, subclinical hemor- 
rhage and others. The reason for this variety of descrip- 
tions is that sometimes only clinical events were used to 
define hemorrhage and in other studies different imaging 
modalities (mainly MRI) had a major impact on the def- 
inition of hemorrhage. We suggest using the established 
Zabramski classification scheme in order to compare dif- 
ferent patient groups and studies. However, the problem 
in defining a hemorrhage is a major reason for the still 
ongoing debate about the risk of hemorrhage and bleed- 
ing rates in patients with cavernomas. 

Most estimates assume that cavernomas are present 
since birth; risk of hemorrhage and bleeding rates are 
mainly based on that assumption. In 1991, Del Curling et 
al. and Robinson et al. were the first to calculate the an- 
nual hemorrhage rate and found that it is between 0.25% 
and 0.7% per patient. Aiba et al. (1995) analyzed patients 
based on the initial finding: if bleeding was the initial 
symptom, the annual hemorrhage rate was 22.9%; if 
seizure was the first symptom, the annual bleeding rate 
was 0.39% per patient. Kondziolka (1995) also stratified 
his patient group into those who had previously experi- 
enced a hemorrhage and those who had not. Patients with 
one previous hemorrhage had a 4.5% yearly risk of hem- 
orrhage, whereas those without a previous hemorrhage had 
a 0.6% yearly risk. An analysis of the symptomatic bleed- 
ing risk in untreated patients who had experienced two or 
more hemorrhages found the rate to be approximately 30% 
per year. Other authors, usually not differentiating between 
initial symptoms, published hemorrhage rates between 
1.1% and 3.1%. Porter et al. reported in 1999 that brain 
stem cavernomas may have a significantly increased risk 
of hemorrhage and calculated it at 5% per person annual- 
ly. Contrarily, Kupersmith and coworkers found a bleeding 
rate of 2.46% in brain stem cavernomas. However, the re- 
bleeding rate - and this is quite well supported by other da- 
ta - was beyond 5% in brain stem cavernomas. All studies 
suggest that the occurrence of rebleeding is an indication 
of a higher bleeding probability of a given cavernoma. The 
risk of a symptomatic rebleed at least doubles in compari- 
son to asymptomatic cavernomas. These findings clearly 




Hemorrhagic Vascular Pathology 



41 



should impact upon therapeutic decisions. The bleeding in- 
cidence is higher in patients with the inherited form of cav- 
emomatosis, however, not for a single given cavernoma, 
but in terms of patient-years. 

Patients younger than 35 years experienced more 
bleeding episodes, and the same was true for those with 
cavernomas of at least 10 mm. A number of studies ad- 
dressed the increased bleeding risk in women; the major- 
ity, however, did not find any gender difference in bleed- 
ing risks. 

The main problem in all these studies is a substantial 
selection bias and the definition of hemorrhage. Another, 
but probably more important aspect for patients when 
discussing bleeding risks is the clinical significance of 
hemorrhage and the probability of a good recovery. The 
probability of a fatal hemorrhage is rather low and many 
patients do have complete or nearly complete recovery 
after the initial bleeding. In general, bleeding rates given 
by surgical groups tend to be higher than those observed 
by others. 

Finally, when discussing the risks of cavernoma with 
patients, it is important to consider that the majority of 
studies calculated an annual risk of 0.5%-l%, much low- 
er than that for true arteriovenous malformations 
(AVMs), and a low risk of fatal hemorrhage. In the ma- 
jority of patients, specifically those older than 35 years, 
harboring a single cavernoma less than 10 mm in diame- 
ter and with seizures as the initial symptom, a wait-and- 
see strategy is reasonable. In patients presenting with an 
initial hemorrhage, the repeat hemorrhage risk is much 
higher, especially if already more than one bleeding event 
has happened. 

As mentioned previously, the majority of patients with 
cavernomas presents with seizures as the initial symp- 
tom. It is important to know that in the vast majority of 
patients, these seizures are not related to acute bleeding 
events, but to hemosiderin deposition adjacent to neu- 
rons. Hemosiderin and ferritin are well-known epilepto- 
genic agents (at least in animal experiments). If surgical 
removal of the cavernoma is considered, understanding 
the relationship between seizures and hemosiderin depo- 
sition is especially important because of pharmacological 
not treatable seizures. It is of utmost importance not on- 
ly to remove those parts of the cavernoma with blood 
flow, but also to remove the hemosiderin ring around the 
cavernoma within the adjacent brain tissue. This part of 
the malformation is responsible for the seizure. 

Due to the slow blood flow, cavernomas are angio- 
graphically occult vascular malformations. If the lesion 
has hemorrhaged, an avascular area with moderate mass 
effect can sometimes be identified. Occasionally (less 
than 10%) a faint blush on the late capillary or early ve- 
nous phase of high-resolution angiograms can be seen. 
Angiography is rarely necessary in typical cavernomas. If 
associated with a developmental venous angioma (DVA), 
presurgical DSA may be indicated to analyze the venous 
drainage pattern. The same is true for those cavernomas 
that do not have the typical MRI appearance. In some of 



these, DSA can increase the diagnostic confidence. On 
CT and, even more, on MRI, imaging features are more 
or less pathognomonic. 

The CT appearance of a cavernoma depends on the 
amount of internal thrombosis, hemorrhage and calcifi- 
cation. The lesions appear hyperdense compared to the 
adjacent brain parenchyma, but can have variable attenu- 
ation values. Because the density of blood on CT depends 
on clot formation, the attenuation of a thrombosed caver- 
noma changes with time. Calcifications do not change 
that much, however, cavernomas tend to calcify only par- 
tially. In patients with a recent hemorrhage, the caver- 
noma may be suspected on CT mainly by taking into ac- 
count the site of hemorrhage and the patient’s history, and 
thus by excluding other typical causes of intracerebral 
bleeding. Differential diagnosis must cover calcified 
brain tumor, mainly oligodendroglioma, which has a high 
tendency of intratumoral bleeding. Contrast enhancement 
can be observed on CT, but usually requires a substantial 
delay between contrast agent injection and scanning. 
Even with a standardized 10-15 minute delay between 
contrast agent injection and scanning, the enhancement 
of a cavernoma varies from none or minimal to striking. 

The imaging modality of choice is MRI. Typically, 
cavernomas have a popcorn-like appearance with a well- 
delineated complex reticulated core of mixed signal in- 
tensities representing hemorrhage in different stages of 
evolution or blood flow at different velocities. Typical is 
a low-signal hemosiderin rim that completely surrounds 
the lesion. The dark signal “blooms” on T2-weighted im- 
ages, and is best visible on gradient echo T2* -weighted 
studies. Brunereau and colleagues studied the sensitivity 
of T2-weighted MRI versus gradient echo (GRE) se- 
quences in patients with the familial form of cavernomas. 
The mean numbers of lesions detected on SE images and 
on GRE images were significantly different (7.2 vs. 20.2 
in symptomatic subjects). Owing to the blood stagnation 
phenomenon or to the presence of true chronic microhe- 
morrhages, cavernous angiomas contain deoxyhemoglo- 
bin or hemosiderin, which generates susceptibility effects 
and decreases signal intensity. This loss of signal intensi- 
ty is much better demonstrated with T2* -weighted GRE 
sequences. This sequence should be part of the imaging 
protocol in all patients with a positive family history of 
cavernoma, a suspicion of focal or generalized seizures, 
or venous angiomas (there is a significant coincidence 
between occurrence of venous angiomas and cavernoma). 
However, turbo spin echo sequences using a long echo 
train, i.e. all FLAIR sequences, are insensitive to this sus- 
ceptibility effect. Furthermore, even large lesions may 
not have a visible hemosiderin ring if there were no rele- 
vant, associated bleeding episodes. 

Arteriovenous Malformations 

Arteriovenous malformations of the brain (brain AVMs) 
correspond to congenital cerebrovascular anomalies, also 




42 



M. Forsting, I. Wanke 



known as intracerebral or pial AVMs. These are not neo- 
plastic lesions; therefore they are not “angiomas”, which 
is obviously an inappropriate term although it is a com- 
monly used. 

Because of the rarity of the disease and the existence 
of asymptomatic patients, establishing a true prevalence 
rate is difficult, and probably not feasible. When consid- 
ering unselected populations, Al-Shahi et al., in a retro- 
spective study in a region of Scotland, found a prevalence 
of 15 per 100 000 living adults over 16 years of age. In 
this series, prevalence was obviously underestimated, 
since it did not consider asymptomatic AVMs. Only large 
post-mortem studies in the general population can give an 
accurate estimate of the prevalence of both symptomatic 
and clinically silent AVMs. However, such a series does 
not exist. Even though brain AVMs are considered to be 
a congenital disorder, nonsystemic familial AVMs are ex- 
tremely rare and only few familial cases have been re- 
ported. No genetic predisposition was found and occur- 
rence of brain AVMs in two members of the same fami- 
ly could have been a fortuitous event. Autopsy data 
showed that only 12% of AVMs are symptomatic while 
the patient is alive and that intracranial hemorrhage was 
the most common clinical presentation. 

Regarding macroscopic pathology, brain AVMs are 
composed of: (1) clustered and abnormally muscularized 
feeding arteries, which may also show changes such as 
duplication or destruction of the elastica, fibrosis of the 
media and focal thinning of the wall; (2) arterialized 
veins of varying size and wall thickness; (3) structurally 
ambiguous vessels formed solely of fibrous tissue or dis- 
playing both arterial and venous characteristics; and (4) 
intervening gliotic neural parenchyma. Brain AVMs anas- 
tomose with normal cerebral vessels. Intracranial hemor- 
rhage is the most frequent clinical presentation of brain 
AVM, with a frequency comprised between 30% and 
82% (Mast, 1995). Overall, the percentages are relative- 
ly close between the different series, with annual rates of 
bleeding between 2% and 4%. 

The occurrence of a first hemorrhage seems to be as- 
sociated with an increased risk of subsequent hemor- 
rhage. In the series of Graf et al., patients with ruptured 
AVMs had a 6% risk of rebleeding in the first year after 
hemorrhage and 2% thereafter. On the basis of retrospec- 
tive analysis, the rupture of brain AVMs is estimated to 
be less severe than that of intracranial aneurysms, with a 
death rate between 10% and 15% and an overall morbid- 
ity rate less than 50% (The Arteriovenous Malformation 
Study Group, 1999). Hemorrhage of brain AVMs can be 
subarachnoid (30%), parenchymal (23%), intraventricu- 
lar (16%) or combined (31%). Parenchymal hemorrhages 
were most likely to result in neurological deficit (52%). 
Overall, in the series of Hartmann (1998), 47% of pa- 
tients had a good outcome after bleeding and an addi- 
tional 37% were independent in daily living. In patients 
with a sudden onset of neurological deficit, CT is usual- 
ly the first imaging modality used, mainly to rule out he- 
morrhage. CT is able to show early parenchymal, sub- 



arachnoid and intraventricular bleeding. The diagnosis of 
brain AVM should be discussed when the patient is 
young, if the parenchymal hematoma has a lobar topog- 
raphy, and if calcifications or spontaneously hyperdense 
serpiginous structures are visible. 

In case of unruptured AVM, unenhanced CT scans 
can be normal. However, in some patients slightly hy- 
perdense serpiginous structures can be seen. Parenchy- 
matous calcifications are observed in 20% of cases re- 
lated to intravascular thrombosis or evolution of an old 
hematoma. Contrast agent injection is absolutely 
mandatory to depict brain AVM on CT. Abnormalities 
of the parenchymal density are visible in approximate- 
ly 25% of cases, related to the presence of gliosis or old 
hematoma. Abnormalities of the ventricular system can 
be observed: focal dilatation in case of associated 
parenchymal atrophy; and compression of the ventricu- 
lar system in case of mass effect caused by the AVM. 
Hydrocephalus can be observed in cases of previous he- 
morrhage or if the ventricular system is compressed by 
enlarged draining veins of the AVM. MRI is currently 
used in cases of unruptured AVM or to find the under- 
lying lesion in cases of lobar hematoma, generally days 
or weeks after bleeding. 

Given the different sequences available, MRI permits 
three levels of analysis of an AVM: 

- Anatomical analysis using conventional sequences, 

- Vascular analysis using MR angiography, and 

- Functional analysis using fMRJ. 

Despite recent developments, CTA and MRA are cur- 
rently not sufficient to obtain a precise description of the 
AVM from an anatomical and hemodynamical point of 
view. Selective angiography is still always necessary to 
make a decision regarding the treatment. In summary, the 
diagnosis of an AVM nowadays is usually based on CT or 
MRI, while the exact and therapeutically relevant 
anatomical and functional information still has to be ob- 
tained by angiography. 

Technically, selective angiography has to be performed 
with a rigorous protocol. To assess as precisely as possi- 
ble the anatomical components of the AVM, it is impor- 
tant to performed selective injection of internal and ex- 
ternal carotid arteries and vertebral arteries. Arterial 
feeders, nidus, and venous drainage are analyzed by per- 
forming multiple projections (anteroposterior, lateral and 
oblique). Three-dimensional angiography may be helpful. 

However, even excellent angiograms are often inade- 
quate for correct therapeutic decisions. The exact anato- 
my of large feeding arteries may be obscure with selec- 
tive injections. Small feeding arteries are sometimes not 
visible on selective angiograms. Although the size of the 
nidus is generally well evaluated by selective angiogra- 
phy, intranidal aneurysms and direct intranidal arteriove- 
nous fistulas are often misdiagnosed. The venous 
drainage of the AVM is generally well studied by selec- 
tive angiography, but the compartments of the AVM and 
their venous drainage are often not depicted, because the 
AVM is injected as a whole. 




Hemorrhagic Vascular Pathology 



43 



For these reasons, superselective angiography often 
gives a more detailed analysis of the AVM and may be- 
come more important in the diagnosis decision. 
Superselective angiography is performed by manual in- 
jection of each separate arterial feeder. It is usually the 
first step of embolization. 



Suggested Reading 

Forsting M (ed) (1994) Intracranial vascular malformations and 
aneurysms: from diagnostic work-up to endovascular therapy. 
Springer, Berlin Heidelberg New York 
Molyneux A, Kerr R, Stratton I, Sandercock P, Clarke M, 
Shrimpton J, Holman R (2002) International Subarachnoid 
Aneurysm Trial (ISAT) of neurosurgical clipping versus en- 
dovascular coiling in 2143 patients with ruptured intracranial 
aneurysms: a randomised trial. Lancet 360:1267-1274 
Ondra SL, Troupp H, George ED et al (1990) The natural history 
of symptomatic arteriovenous malformations of the brain: a 
24-year follow-up assessment. J Neurosurg 73:387-391 



Pollock BE, Flickinger JC, Lunsford LD et al (1996) Factors that 
predict the bleeding risk of cerebral arteriovenous maforma- 
tions. Stroke 27:1-6 

Porter RW, Detwiler PW, Spetzler RF, Lawton MT, Baskin JJ, 
Derksen PT et al (1999) Cavernous malformations of the brain- 
stem: experience with 100 patients. J Neurosurg 90(l):50-58 
Rigamonti D, Hadley MN, Drayer BP, Johnson PC, Hoenig- 
Rigamonti K, Knight JT, Spetzler ^ (1988) Cerebral cav- 
ernous malformations. Incidence and familial occurence. N 
EnglJ Med 319:343-347 

Robinson JR, Awad lA, Little JR (1991) Natural history of the cav- 
ernous angioma. J Neurosurg 75:709-714 
Spetzler RF, Martin NA (1986) A proposed grading system for ar- 
teriovenous maformations. J Neurosurg 65:476-483 
Wiebers DO, Whisnant JP, Huston J 3rd, Meissner I, Brown RD Jr, 
Piepgras DG, Forbes GS, Thielen K, Nichols D, O’Fallon WM, 
Peacock J, Jaeger L, Kassell NF, Kongable-Beckman GL, 
Tomer JC (2003) Unmptured intracranial aneurysms: natural 
history, clinical outcome, and risks of surgical and endovascu- 
lar treatment. Lancet 362:103-110 
White PM, Wardlaw JM, Easton V (2000) Can noninvasive imag- 
ing accurately depict intracranial aneurysms? A systematic re- 
view. Radiology 217:361-370 




IDKD 2004 



Demyelinating Diseases 

K.K. Koeller', R.G. Ramsey^ 

^ Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC, USA 
2 Premier Health Imaging, Chicago, IL, USA 



Introduction 

The spectrum of white matter diseases is broad, with con- 
ditions ranging from the relatively benign to the progres- 
sively debilitating to the rapidly fulminant and fatal. 
While a specific diagnosis based on the imaging appear- 
ance alone is often not possible because of considerable 
overlap among the diseases, magnetic resonance imaging 
(MRI) remains ideal for the detection of many of these 
diseases because of its sensitivity in identifying free wa- 
ter within the normally myelinated white matter. 

The oligodendrocyte, located predominantly within 
the white matter, is the cell responsible for the production 
of myelin and is also the least common of the three ma- 
jor cells (after neurons and astrocytes) that compose the 
brain parenchyma. Demyelinating diseases are not char- 
acterized by neoplastic growth. Rather, the attack on the 
oligodendrocyte leads to a loss of myelin. Consequently, 
the hallmark imaging manifestation of a demyelinating 
process is a white matter lesion with T2 hyperintensity 
that produces little mass effect for the size of the lesion. 
This brief review focuses on the classic demyelinating 
process, multiple sclerosis, and other demyelinating con- 
ditions arising from viral infection, chronic toxic condi- 
tions, iatrogenic causes, vascular disease, and inherited 
metabolic white matter disease. 



Primary Demyelination 

The prototypical white matter disease is multiple sclero- 
sis (MS). Despite the more than 160 years since the first 
clinical features of the disease were recognized in 1837 
by Carswell and Cruveilhier, much of this demyelinating 
process is not well understood. Although many etiologies, 
including trauma and viral infection, have been proposed, 
many authorities now believe that the disease is primari- 
ly autoimmune in nature and modulated by genetic fac- 
tors (chromosome 6). This hypothesis is supported by the 
frequent association of MS with many other autoimmune 
conditions (e.g. Graves’ disease, myasthenia gravis, 
Crohn’s disease, systemic lupus erythematosus). 



The incidence of MS varies with geography, with in- 
creased frequency of the disease in cooler climates. In the 
United States and countries of northern Europe, the inci- 
dence is about 1 per 1000. MS is primarily a disease of 
young and middle-aged adults (95% of cases occur in pa- 
tients between the ages of 18 and 50 years) and it is the 
second most common disabling disease of young adults, 
with only acquired immune deficiency syndrome (AIDS) 
being more common. Most (60%) patients with the dis- 
ease are female [1]. 

Typical clinical presenting symptoms include pares- 
thesia, numbness, diplopia, weakness, gait disturbance, 
and burning sensations. About 7% of patients present 
with symptoms reflecting myelitis in which hemiparesis, 
constipation, urinary retention, or incontinence are typi- 
cal features. Seizure activity occurs in about 5% of cas- 
es. Uthoff ’s phenomenon gained prominence decades ago 
as a provocative test for MS, based on the observation 
that patients with MS have a worsening of their symp- 
toms when they are exposed to warm temperatures. The 
test was abandoned when it was noted that some patients 
would not return to their neurologic baseline. MS is 
rarely seen in children, especially before the age of pu- 
berty. Clinical exacerbations in women are common in 
the first 6 months of the post-partum period. Detection of 
oligoclonal gammopathy on cerebrospinal fluid examina- 
tion is an important laboratory finding but may not al- 
ways be present [2]. 

The phenomenon of optic neuritis, characterized clin- 
ically by retrobulbar pain, a central monocular loss of vi- 
sion, and an afferent papillary defect (Marcus Gunn 
pupil) is especially useful as a clinical hallmark for MS. 
The likelihood of a female patient with optic neuritis hav- 
ing MS, either at the time of presentation or sometime in 
the future, is 74%. While the diagnosis is best substanti- 
ated by clinical inspection, magnetic resonance imaging 
remains valuable in directing therapy. When 2 or more 
MS-like lesions are noted, intravenous eortieosteroid 
therapy is advocated and may slow the development of 
full-blown MS [3]. 

The clinical criteria required to establish the diagnosis 
are complex and require strict implementation to be ef- 




Demyelinating Diseases 



45 



fective [4]. In general, two distinctly different clinical “at- 
tacks” from two different lesions in the central nervous 
system are required to make the diagnosis, although 
many variations on this theme are possible with adjunc- 
tive laboratory and imaging findings. Three forms of the 
disease are recognized: relapsing-remitting, progressive, 
and monosymptomatic [5]. The majority (70%) of pa- 
tients with MS present clinically with the relapsing-re- 
mitting form of the disease. Typical symptoms include 
numbness, dysesthesia, and burning sensations. A patient 
must have at least 2 clinical attacks from two clinically 
distinct lesions. The episodes must be for at least 24 
hours duration and be at least 30 days apart [4]. Partial or 
complete remission for months or years is expected for 
patients with this form. 

The second most common form of MS is the progres- 
sive form, affecting about 20% of patients, and it is fur- 
ther subdivided into primary and secondary subtypes. In 
the primary progressive form of the disease, the clinical 
presentation is marked by a slow onset without the dis- 
tinct attacks that are typical for the relapsing-remitting 
form. In the secondary progressive form, the patient pre- 
sents initially in the relapsing-remitting form with later 
transformation into progressively worsening disability in 
addition to individual clinical relapses. 

The most controversial form is the “monosymptomatic 
demyelinating” form occurring in about 10% of MS pa- 
tients. Patients with this form have one or two episodes 
of characteristic symptoms, followed by complete recov- 
ery to their neurologic baseline. By its very nature, it is 
clearly an unusual form of MS and some authorities 
question whether it is truly part of the MS family but may 
instead be an entirely distinct clinicopathologic disease. 

Several variant types of MS have been identified. An es- 
pecially aggressive form, known as acute fulminant MS of 
the Marburg type, manifests with a rapidly progressive 
neurologic deterioration from severe axonal loss, leading 
to death within a few months [6]. Another variant, neu- 
romyelitis optica (Devic’s disease), is characterized by both 
visual and myelopathic symptoms because of involvement 
of the optic nerve and spinal cord. Balo concentric sclero- 
sis is a variant form characterized by alternating concen- 
tric bands of demyelination and normal myelination. These 
features are not only noted histologically but are also well 
seen on cross-sectional imaging studies [7]. 

Pathologically, MS is an inflammatory process with 
focal hypercellularity from microglial infiltration com- 
bined with perivascular cuffing of lymphocytes marking 
the acute phase of a sclerose en plaque or MS plaque. In 
this phase, the oligodendrocyte - the cell responsible for 
the production of myelin - is most affected by these 
changes and results in the overall loss of myelin. The 
plaque, which has a predilection for the periventricular 
zone, may be either active, characterized by inflammato- 
ry changes with breakdown of the blood-brain barrier, or 
inactive, characterized by gliosis and complete loss of 
myelin. Later on, destruction of axons leads to parenchy- 
mal loss and cerebral atrophy. 



Magnetic resonance imaging (MRI) is the modality of 
choice for the evaluation of patients suspected of having 
MS and is an essential tool in assessing the natural course 
of the disease and effects of treatment. MRI frequently 
identifies many lesions that are not suspected from clin- 
ical examination [8]. Small focal hyperintense lesions, 
particularly in a periventricular distribution, with rela- 
tively less mass effect for the size of the lesion charac- 
terize the disease on T2-weighted images [9]. Many MS 
lesions are ovoid in shape with their long axis perpendic- 
ular to the ventricular wall, corresponding to the pathway 
of periventricular white matter vessels, and corroborate a 
pathologic feature, known as Dawson’s finger [10]. An 
especially important location for MS plaques is the cor- 
pus callosum-septum pellucidum interface. The detection 
of lesions at this site carries increased specificity for the 
diagnosis of MS [11]. Fluid-attenuated inversion recov- 
ery (FLAIR) imaging is particularly helpful in identify- 
ing periventricular lesions, although lesions of the brain 
stem and cerebellum may be less obvious with this tech- 
nique because of susceptibility effects [12]. 

On initial inspection, the imaging appearance of some 
large plaques may mimic that of a brain tumor. Closer 
evaluation reveals the relative lack of mass effect for the 
size of these “tumefactive” MS plaques and provides a 
valuable clue to the correct diagnosis [13]. Distinction 
between plaques in the active phase and plaques in the 
chronic phase can be made with contrast-enhanced MRI 
as active plaques enhance while chronic plaques do not 
[9, 14]. The enhancement correlates with the presence of 
inflammatory cells and signifies the loss of a normal 
blood-brain barrier [9]. 

In the advanced stages of the disease, cerebral atrophy 
is noted on MRI studies with prominent ventricu- 
lomegaly and sulcal enlargement and appears to be more 
common in patients with the secondary progressive form 
of the disease than in patients with the relapsing-remit- 
ting form [15]. The presence of cerebral atrophy, as evi- 
denced by thinning of the corpus callosum and enlarge- 
ment of the third ventricle width, or by using computer- 
aided techniques, correlates better with clinical disability 
than the number of lesions on T2-weighted images [15, 
16]. Advanced MRI techniques are providing even more 
information about the nature of the MS plaque and hold 
the promise of better assessment of the effects of thera- 
py. Magnetization transfer imaging reveals differences in 
magnetization transfer between MS plaques and other 
white matter lesions, such as senescent white matter le- 
sions [17]. On MR spectroscopy, a decreased peak of N- 
acetylaspartate (NAA), decreased NAA:creatine ratio, 
and an increased choline: creatine ratio have been seen in 
both active and chronic plaques, although the incidence 
varies among the different clinical types of the disease. 
Increased amounts of choline, lipids, lactic acid, and in- 
ositol have also been variably reported and highlight the 
dynamic nature of the MS plaque [18, 19]. Recently, MR 
perfusion studies have shown regions of decreased perfu- 
sion, believed to represent areas of hemodynamic and mi- 




46 



K.K. Koeller, R.G. Ramsey 



crovascular abnormality, in patients with MS even though 
no abnormal T2 hyperintensity was noted on other MR 
sequences. This supports the belief that MS is truly a dif- 
fuse white matter disease, with more involvement beyond 
readily identifiable plaques. 

About 7% of all MS cases involve the spinal cord. MS 
plaques in this territory tend to involve 2 or more verte- 
bral body segments, compared to transverse myelitis, 
which is usually limited to one vertebral body segment. 
MS myelitis also tends to involve the dorsal columns. 
Most (60%) patients with spinal cord MS plaques have 
cerebral plaques as well. 

Despite all of these imaging features, it is important to 
emphasize two/‘truths” about MS. First, the MS plaque 
is a dynamic entity, not only fluctuating between an ac- 
tive phase and a chronic phase but also showing remyeli- 
nation, inflammatory changes, gliosis, and demyelination 
at any given time. Second, the diagnosis of MS is still on- 
ly established with clinical correlation. None of the imag- 
ing presentations, either alone or in combination, de- 
scribed previously is pathognomonic. The diagnosis of 
MS carries a tremendous emotional undercurrent for the 
patient. With this in mind, the radiologist should strictly 
avoid labeling a patient as “having MS” in a radiological 
report in the absence of clinical confirmation. 

White Matter Disease from Viral Infection 

Acute Disseminated Encephalomyelitis 

Acute disseminated encephalomyelitis (ADEM) is a de- 
myelinating disease that is typically seen 1-3 weeks after 
patients are vaccinated or have a viral infection. 
Neurologic symptoms in ADEM vary from mild 
(headache and meningeal signs) to severe (neurologic 
deficits and coma). In contrast to MS, ADEM is a 
monophasic illness and children are more commonly af- 
fected. Since ADEM is a diagnosis of exclusion, long- 
term follow-up is required to completely exclude MS. 
Most (80%) patients have a good prognosis but 10%-20% 
have a persistent neurologic deficit. Rarely, the disease 
ean result in death. It is believed that ADEM represents 
an autoimmune response that triggers perivenous de- 
myelination in immunocompetent patients. No virus or 
bacterium has been isolated in any patient with ADEM on 
autopsy examination. A rare hyperacute aggressive form, 
acute hemorrhagic leukoencephalitis, may occur in chil- 
dren and is usually fatal, secondary to herniation. 

On computed tomography (CT), ADEM may not be 
detected or it may have an ill-defined non-specific hy- 
poattenuation. On MRI, the lesions of ADEM are fre- 
quently asymmetric, varying in size and number, with lit- 
tle or no mass effect, a hallmark feature of a demyelinat- 
ing process. Variable enhancement is seen on contrast-en- 
hanced studies. Similar to MS, lesions may oecasionally 
involve the optic nerve or spinal cord [20]. 



Progressive Multifocal Leukoencephalopathy 

Progressive multifocal leukoencephalopathy (PML) is 
overwhelmingly a disease of the immunocompromised 
patient population and most (55%-85%) eases are related 
to AIDS. There is a wide age range of involvement, with 
the peak age of presentation in the sixth decade. The dis- 
ease is caused by reactivation of a papovavirus (JC virus) 
that selectively attacks the oligodendrocyte, leading to 
demyelination. In contrast to patients with ADEM, pa- 
tients with PML have an extremely poor prognosis, with 
death common in the first 6 months following establish- 
ment of the diagnosis. 

Like ADEM, the lesions of PML display little mass ef- 
fect or enhancement. Rarely, some lesions may be large 
enough to be assoeiated with some mass effect and, in 
these circumstances, it may be difficult to differentiate 
them from true neoplasms. Most lesions involve the sub- 
cortical white matter and deep cortical layers of the pari- 
eto-occipital or frontal white matter, although gray matter 
and posterior fossa lesions may occur in up to 50% of cas- 
es. PML lesions tend to be more confluent in their appear- 
ance than ADEM lesions. Scalloping of the lateral margin 
of the lesion at the gray-white matter junction is common. 
Occasionally, the lesions contain hemorrhage [21]. 

Human Immunodeficiency Virus Encephalopathy 

Human immunodeficiency virus (HIV) encephalopathy 
results from direct infection of the brain by the virus it- 
self. Most patients are severely immunocompromised at 
the time of onset and exhibit psychomotor slowing, im- 
paired mental status, and memory difficulties. 
Histologically, demyelination and vacuolation with axon- 
al loss are noted, along with occasional microglial nod- 
ules. Mild cerebral atrophy is the first and sometimes on- 
ly imaging feature of the disease, which is also known as 
AIDS dementia complex, HIV dementia, and HlV-asso- 
eiated dementia complex. Involvement of the eentral 
white matter, basal ganglia, and thalamus is eharaeteris- 
tic. Typically, bilaterally symmetric areas of abnormal hy- 
perintensity in the basal ganglia and small focal areas in 
the periventricular regions are noted on T2-weighted MR 
images. Regression of these findings has been seen fol- 
lowing institution of antiretroviral therapy [22]. 

White Matter Disease from Toxic Imbalance 

Chronic Alcohol Ingestion and its Consequences 

Chronic alcohol ingestion predominantly causes atrophy 
that involves the entire cerebral hemisphere and the su- 
perior cerebellar vermis. Two diseases - Marchiafava- 
Bignami disease and Wernicke’s encephalopathy - in- 
volve necrosis of distinct locations and are important 
consequences of chronic alcoholism. Selective demyeli- 
nation and necrosis of the corpus callosum is the hall- 




Demyelinating Diseases 



47 



mark of Marchiafava-Bignami disease. Originally de- 
scribed by two Italian physicians who documented the 
disease in a series of poorly nourished patients who died 
from the effects of excessive consumption of Italian red 
wine, Marchiafava-Bignami disease can occur in any 
population and from any alcoholic agent. It has even been 
reported in poorly nourished non-drinkers. The necrotic 
zones are especially well seen as abnormal hyperintense 
foci on sagittal T2-weighted images. If the patient sur- 
vives, atrophy of the corpus callosum is seen [23]. 

Wernicke’s encephalopathy causes necrosis in the me- 
dial thalamic nuclei and mamillary bodies, which results 
from thiamine deficiency. Patients with the disease typi- 
cally present with ophthalmoplegia, ataxia, and confu- 
sion. The disease is uniformly fatal unless replacement 
thiamine therapy is instituted within 24-72 hours of pre- 
sentation. Abnormal T2 hyperintensity within the medial 
portions of the thalami is the hallmark imaging feature of 
this disease. While the thalamic changes are potentially 
reversible, atrophy of the mamillary bodies is permanent. 

Osmotic Myelinolysis 

Formerly called “central pontine myelinolysis”, the term 
“osmotic myelinolysis” was proposed a few years ago to 
emphasize the nature of this disease: rapid intravascular 
osmotic change causes endothelial injury in the regions 
where the gray and white matters are most closely ap- 
posed, i.e. in the central portion of the pons. The end re- 
sult of this endothelial injury is demyelination. Clinical 
symptoms usually include acute mental status changes, 
lethargy, dysphagia, and progressive quadriparesis. Once 
thought to be uniformly fatal, it is now known that this is 
not necessarily true and a return to a normal imaging ap- 
pearance and clinical status may be seen over a variable 
period of time. The classic imaging appearance of os- 
motic myelinolysis is hypoattenuation on CT and T1 and 
T2 prolongation on MRI within the center of the pons. 
Distinctive sparing of the pons periphery is noted. 
Extrapontine involvement may be noted in about 10% of 
cases and usually involves the basal ganglia and others 
locations within the brain [24]. 

White Matter Disease Associated with 
Radiation Therapy and Chemotherapy 

Radiation Injury and Necrosis 

The spectrum of radiation injury to the brain is broad. 
Three distinct categories of disease are noted: acute radia- 
tion injury, early delayed radiation injury, and late radia- 
tion injury. In acute radiation injury, mild transient en- 
cephalopathic symptoms present very shortly after initia- 
tion of radiation. No CT or MRI findings are seen with 
this form of injury. Early delayed radiation injury produces 
demyelination within the white matter at least 2 months af- 
ter the start of radiation therapy. Lesions predominate in 



the white matter, basal ganglia, and cerebral pedimcles. 
Late radiation injury has 3 different forms: focal radiation 
necrosis, diffuse radiation injury, and necrotizing leukoen- 
cephalopathy. While the first two generally occur at least 
one year after the start of therapy, the last entity may man- 
ifest as early as 3 months after onset of therapy [25]. 
Distinguishing radiation necrosis from reciurent malig- 
nant brain tumor, such as glioblastoma multiforme, is fre- 
quently impossible using conventional MRI. Both lesions 
may have mass effect and surrounding vasogenic edema, 
and may enhance on contrast-enhanced studies. Metabolic 
imaging (e.g. positron emission tomography) or MR spec- 
troscopy (MRS) may facilitate differentiating between the 
two possibilities. Radiation necrosis is iso- to hypometa- 
bolic on metabolic imaging studies and has a characteris- 
tic lactic acid peak and near-normal peaks for TV-acetylas- 
partate (NAA) and choline on MRS. In contrast, recurrent 
high-grade gliomas are hypermetabolic and typically show 
elevated choline levels compared to NAA without or with 
elevated lactic acid levels. 

Diffuse radiation injury is characterized by white mat- 
ter changes that are “geographic” in nature, i.e. the areas 
of abnormal signal intensity or attenuation are limited to 
the regions of the brain that correspond to the radiation 
portal. This can produce striking differences between the 
involved zones and the spared surrounding white matter. 
The involved territories are often symmetric and do not 
enhance on post-contrast studies. 

While originally reported in children with leukemia, 
diffuse necrotizing leukoencephalopathy has also been 
observed following treatment for many other malignan- 
cies in both children and adults. The disease may occur 
following chemotherapy alone but the incidence of dis- 
ease is highest when chemotherapy is combined with ra- 
diation therapy. Both the histologic findings and imaging 
features bear resemblance to radiation necrosis. Axonal 
swelling, demyelination, coagulation necrosis, and gliosis 
dominate the histologic picture. Diffuse white matter 
changes, with hypoattenuation on CT and T1 and T2 pro- 
longation on MRI, are common and often involve an en- 
tire hemisphere [26]. 

Mineralizing Microangiopathy 

Usually seen in children with cancer who have been treat- 
ed with chemotherapy alone or in combination with radi- 
ation therapy, mineralizing microangiopathy results from 
deposits of calcium in and around small penetrating 
blood vessels of the deep brain leading to local areas of 
necrosis. This is the most common neuroradiologic ab- 
normality noted in this group of patients. The disease has 
a predilection for the basal ganglia, especially the puta- 
men, and, more rarely, the cerebral cortex. On CT and 
MRI, evidence of cortical atrophy, abnormal attenuation 
and signal intensity changes within the white matter are 
typically noted. Of all chemotherapeutic agents, 
methotrexate is the one classically associated with min- 
eralizing microangiopathy. Patients younger than 5 years 




48 



K.K. Koeller, R.G. Ramsey 



of age who have meningeal leukemia and have received 
high-dose methotrexate therapy are at greatest risk for de- 
veloping this complication of therapy [27]. 

Vascular Causes of White Matter Disease 

Posterior Reversible Encephalopathy Syndrome 

Under normal circumstances, cerebral perfusion pressure 
is maintained at a relatively constant level by autoregula- 
tion, a physiologic mechanism that compensates for wide 
changes in systemic blood pressure. Hypertensive en- 
cephalopathy is believed to result from loss of normal au- 
toregulation, with competing regions of vasodilatation and 
vasoconstriction as a result. Current theory espouses that 
the vessels of the posterior cerebral circulation, having 
less sympathetic innervation compared to those of the an- 
terior circulation, are unable to vasoconstrict in a normal 
manner and therefore bear the brunt of these vascular 
changes. Accordingly, visual field deficits are common, as 
are headaches, somnolence, and an overall impaired men- 
tal status. Since this hypertensive encephalopathy is also 
reversible if treated promptly, it has been referred to as 
posterior reversible encephalopathy syndrome (PRES). 
The disease is also associated with renal failure, pre- 
eclampsia, eclampsia, and the use of immunosuppressive 
agents such as cyclosporin A and FK506. 

On MRI studies, abnormal T2 hyperintensity is most 
commonly seen in the distribution of the posterior circu- 
lation, although other sites including the frontal lobes and 
corpus callosum may be noted as well. Frequently, the le- 
sions are bilaterally symmetric. Diffusion- weighted 
imaging may be normal or show restricted water diffu- 
sion while perfusion studies indicate normal to increased 
perfusion in these zones. When biopsy of these regions is 
performed, white matter edema is seen histologically. 
Following treatment or removal of the offending im- 
munosuppressive agent, the lesions resolve and the in- 
volved sites return to normal signal intensity [28]. 

Ischemia and Vascular Disease 

Small focal lesions of T2 hyperintensity are quite com- 
mon in the white matter of adult patients. They are not as- 
sociated with mass effect, do not enhance, and are typi- 
cally isointense compared to normal white matter on Tl- 
weighted images. When these lesions have been biopsied, 
histologic examination reveals a wide range of findings 
including gliosis, loss of myelination, and areas of is- 
chemia. Senescent white matter lesions tend to be locat- 
ed in the periventricular white matter (although not im- 
mediately adjacent to the ventricular margin), centrum 
semiovale, and optic radiation. In contrast to MS lesions, 
they do not involve the corpus callosum, an important 
distinguishing feature. Since the lesions are so ubiquitous 
and appear to be a part of “normal” aging, various terms 
have been proposed: senescent white matter changes or 



disease, deep white matter ischemia, etc. In general, the 
more lesions present, the more likely it is that the patient 
will have cognitive problems or difficulties with neu- 
ropsychologic testing. However, it is not possible to pre- 
dict a particular patient’s status simply based on the imag- 
ing appearance alone. Hence, the diagnosis of 
Binswanger’s dementia should be avoided unless sub- 
stantiated with clinical evidence. 

The presence of periventricular and subcortical lesions 
in an adult 30-50 years of age, with a family history of 
similarly affected relatives, should raise the possibility of 
cerebral autosomal dominant arteriopathy with subcorti- 
cal infarcts and leukoencephalopathy (CADASIL). A de- 
fect on the long arm of chromosome 19 has been identi- 
fied and apparently evokes an angiopathy affecting small 
and medium-sized vessels. Most lesions occur in the 
frontal and temporal lobes. Less commonly, the thalamus, 
basal ganglia, internal and external capsules, and brain 
stem may be involved [29]. 

Many other conditions and diseases are associated 
with small vessel injuries that commonly involve the 
white matter as small, focal areas of abnormal T2 hyper- 
intensity. These include autoimmune disease, particularly 
systemic lupus erythematosus, Behget’s disease, and gi- 
ant cell arteritis, as well as arteritis associated with drug 
use (e.g. metamphetamine and heroin), radiation injury, 
and malignancy. 

Dysmyelinating and Metabolic Diseases 

The number and understanding of inherited metabolic 
white matter diseases have exponentially increased in the 
last 50 years and continue to expand yearly. Most will 
manifest in childhood, especially during infancy, and 
many are transmitted in an autosomal recessive fashion. 
Imaging features in these diseases are rarely pathogno- 
monic and practically all require biochemical analysis of 
blood, urine, and skin to establish the diagnosis. From a 
pathophysiologic basis, these disorders are categorized 
based on the cellular organelle in which the altered me- 
tabolism is located. Lysosomal disorders, or “storage 
disorders”, are a clinically heterogeneous group caused 
by an enzyme deficiency that results in the accumulation 
of phospholipids, glycolipids, mucopolysaccharides, or 
glycoproteins, all of which interfere with myelin pro- 
duction. Peroxisomal disorders are caused by an enzyme 
deficiency within peroxisomes, an organelle that is par- 
ticularly common in oligodendrocytes, and alter normal 
lipid metabolism with the accumulation of very long- 
chain fatty acids. The mitochondrial disorders are a clin- 
ically heterogeneous group of diseases that result in 
spongy degeneration of myelin in various locations and 
also frequently involve muscles. Amino and organic acid 
disorders are rare and the clinical presentation is depen- 
dent on which acid is involved. Special types of leukody- 
strophies compose the last group. These represent those 
that are associated with macrocrania (Canavan’s disease, 
Alexander’s disease) or sudanophilic deposits noted on 




Demyelinating Diseases 



49 



histologic examination (Cockayne’s disease, Pelizaeus- 
Merzbacher disease) [30]. 

Diseases that tend to involve the “central” white matter 
first include Krabbe’s disease, X-linked adrenoleukodys- 
trophy and other peroxisomal disorders, metachromatic 
leukodystrophy, and Pelizaeus-Merzbacher disease. 
Diseases that tend to involve the peripheral white matter 
first include Alexander’s disease, Canavan’s disease, and 
Cockayne’s disease. Diseases that involve gray matter in 
addition to the white matter involvement include mito- 
chondrial disorders and the mucopolysaccharidoses. If 
hemorrhage is seen within a white matter lesion on an 
imaging study, it should provoke consideration of a diag- 
nosis other than an inherited metabolic disorder. 

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IDKD 2004 



Brain Degeneration and Aging 

M.A. van Buchem 

Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands 



Introduction 

Many diseases result in degeneration of the nervous sys- 
tem. To name a few; infection, multiple sclerosis, and tu- 
mors destroy neuronal tissue. However, the term neu- 
rodegenerative disorders refers to a group of diseases that 
share the characteristic of death of subsets of specific 
classes of neurons. Another common feature of the class 
of neurodegenerative disorders is the fact that they are id- 
iopathic, the etiology of these diseases is not completely 
understood. With increasing knowledge of the pathogen- 
esis of these diseases, disorders that are presently classi- 
fied as neurodegenerative will be grouped among dis- 
eases with a known pathogenesis, and consequently, the 
list of degenerative disorders will decrease. This paper 
discusses the neuroradiological aspects of a number of 
disorders that are presently considered to be neurodegen- 
erative. 



Normal Aging 

The most coimnon neurodegenerative disorder is aging. 
Aging is associated with degenerative changes of the 
brain. With increasing life expectancy of the population, 
the number of elderly persons increases in industrialized 
societies. Therefore, radiologists in such societies will in- 
creasingly be confronted with age-related changes in the 
brain. Knowledge of these changes is thus essential for 
every radiologist. 

Before describing the abnormalities that occur with 
aging, it is important to be aware of a few facts. First, 
age-related abnormalities do not occur in all elderly per- 
sons. Some elderly individuals have a perfectly normal 
brain that is indistinguishable from that of a young per- 
son. This observation is in line with the concept of sub- 
dividing human aging in successful aging and usual ag- 
ing. Successful aging is defined as minimal physiologic 
loss, even when compared with younger individuals, 
while usual aging is the presence of disturbance of phys- 
iologic functions (such as systolic hypertension, abnor- 
mal glucose tolerance) without overt neurologic symp- 



toms. Elderly individuals with a normal appearance of 
the brain on imaging may be representatives of the group 
of successfully aging human beings. 

Second, age-related changes that are apparent on radi- 
ological examinations do not always have functional con- 
sequences. An impressive load of brain lesions may be an 
incidental finding in an elderly individual who has no 
neurological or intellectual complaints whatsoever and 
who, apparently, is capable of having a normal, indepen- 
dent life. 

Third, normal aging and neurodegenerative disorders 
may be difficult to distinguish. One reason is the similar- 
ity of the abnormalities that are associated with these 
conditions. In several neurodegenerative disorders, the 
abnormalities only differ in pattern from those occurring 
in normal aging. In other neurodegenerative disorders, 
the abnormalities really are similar, also in pattern, and 
the amount of abnormalities in relation to a patient’s age 
is the only factor that permits distinction from normal ag- 
ing. Another phenomenon that complicates distinguish- 
ing normal aging from other neurodegenerative disorders 
is the fact that due to the high prevalence of the latter, 
these conditions often coexist in the elderly with changes 
that are due to normal aging. In such circumstances it 
may be impossible to separate the abnormalities in terms 
of their origin. 

An important task for radiologists, when confronted 
with a brain study in an elderly patient, is to screen for 
the presence of neurodegenerative disorders. In this 
process, changes should not be attributed too easily to 
normal aging. In order to be able to separate usual aging 
and other neurodegenerative disorders, a radiologist 
should be familiar with the changes that occur in normal 
aging. In the following section such changes are de- 
scribed. 

Atrophy 

With normal aging, mild to moderate atrophy of the brain 
occurs. This is mainly due to a gradual loss of white mat- 
ter, based on loss of myelinated fibers and thinning of 
capillary walls. Since, the cerebrospinal fluid (CSF) com- 




Brain Degeneration and Aging 



51 



pensates for the decreasing volume that the brain occu- 
pies in the skull, the CSF space directly reflects brain at- 
rophy. CSF spaces that are to be evaluated when screen- 
ing for signs of atrophy are the pericerebral and pericere- 
bellar spaces, the caliber of the ventricles, and the pres- 
ence and size of Virchow-Robin spaces (VRS). 

In both radiologic and pathologic studies it has been 
demonstrated that progressive enlargement of the ventri- 
cles, cerebral sulci, and cerebellar CSF space occurs with 
aging. From 10 to 50 years of age, the CSF-to-brain ratio 
remains constant. In the fifth decade the contribution of 
CSF to the intracranial volume starts increasing. However, 
this increase is highly variable, and in 30%-50% of the el- 
derly the CSF space remains in the range of those of 
young adults. Furthermore, in a large community-living, 
elderly population, sex differences have been demonstrat- 
ed for the association of age and atrophy. In elderly men, 
atrophy is more pronounced than in elderly women. 

In general, the increase of CSF space that is associat- 
ed with normal aging occius diffusely. However, in spe- 
cific locations atrophy is more pronounced on imaging 
studies. An early finding may be third ventricular en- 
largement, due to atrophy of the median nuclei of the 
thalamus. The temporal horns of the lateral ventricles en- 
large only mildly with normal aging. Widening of the 
cortical sulci occurs first in the frontal and parietal 
parasagittal regions, whereas the sulci in the central, pre- 
central, post-central, and superior frontal g 3 ui widen lat- 
er in life. The frontal interhemispheric fissure and the 
CSF space around the cerebellar vermis are often 
widened clearly in normal elderly. The anterior portion of 
the sylvian fissure widens earlier than the posterior part. 
Moreover, in all age groups, the left sylvian fissure and 
left lateral ventricle are generally wider than their equiv- 
alents on the right side. 

Another reflection of atrophy in the elderly is in- 
creased visibility of VRS. VRS are an extension of the 
subarachnoid space around perforating vessels that extent 
up to the level of the capillaries. Consequently, these 
perivascular spaces are filled with CSF. Local dilatations 
of VRS occur in all age groups, and are considered a nor- 
mal anatomical variant. Such dilatations may render them 
visible on computed tomography (CT) and magnetic res- 
onance imaging (MRI). On cross-sectional images, VRS 
appear as sharply delineated round, oval, or curvilinear 
structures that have no mass effect. The content of VRS 
follows the characteristics of CSF on CT and on all pulse 
sequences of MRI. VRS have sites of predilection: in the 
basal ganglia at the level of the anterior commissure, in 
the convexity, in the subinsular cortex, and in the mid- 
brain. At these sites VRS often occiu bilaterally and sym- 
metrically. With advancing age, the number and size of 
VRS that are visible on cross-sectional imaging increase, 
in particular at the convexity and less so in the basal gan- 
glia. Etat crible is an extreme form of dilated VRS that 
may occur in aging. Age-related widening of VRS has 
been considered a manifestation of atrophy of the brain, 
similar to the increased pericerebral CSF space enlarge- 



ment. In addition, it has been attributed to increased tor- 
tuosity of penetrating arteries and arterioles that is asso- 
ciated with aging. 

Since atrophy often is a global process, it may be dif- 
ficult to assess qualitatively on cross-seetional images 
whether atrophy of the brain is present or not. Evaluation 
of the volume of the corpus callosum on a mid-sagittal 
image is easier. Since the corpus callosum generally re- 
flects brain volume and thus atrophy, looking at the cor- 
pus callosum may help detecting atrophy. 

Gray Matter Hypointensities 

On MRI, the signal intensity of the deep gray matter nu- 
elei changes with age. These changes comprise lowering of 
the signal intensity on T2-weighted images. It has been 
postulated that the substrate for these changes is an in- 
creasing deposition of ferritin, a storage form of non-heme 
iron. The visibility of these changes depends on field 
strength and specifications of the MRI sequence used. 

In the first 10 years of life, the signal intensity of the 
deep gray matter nuclei on T2-weighted images is sim- 
ilar to that of the cerebral cortex. By age 25 years, the 
signal intensities at 1.5 tesla of the globus pallidus, red 
nucleus and pars reticulata of the substantia nigra be- 
come hypointense to the cortical gray matter and white 
matter. At that age, the dentate nucleus has low signal 
intensity in only one-third of cases. With aging, the hy- 
pointensity is relatively constant in the red nucleus, sub- 
stantia nigra, and dentate nucleus. However, the volume 
of hypointensity in the globus pallidus increases with 
aging. In the putamen, hypointensity is only found in 
the elderly population (older than 60 years of age), and 
may equal that in the globus pallidus in the eighth 
decade. In the healthy elderly, hypointensity on T2- 
weighted images is never found in the caudate nucleus 
and thalamus. Hypointensity in these structures in el- 
derly suggests disease. 

White Matter Hyperintensities 

With age the prevalence of focal lesions in white matter 
increases. These lesions can be subdivided in dilated 
VRS, infarct-like lesions, and aspecific white matter le- 
sions. VRS have been discussed earlier in this document, 
and are characterized by a signal intensity that follows 
that of CSF on all pulse sequences. Infarct-like lesions 
have been defined as focal, non-mass areas; they are hy- 
perintense to gray matter on proton density-weighted 
and T2-weighted images and have signal intensities that 
approximate that of CSF on T1 -weighted images. 
Aspecific white matter lesions are those non-mass le- 
sions with high signal intensity on proton density- 
weighted-images and T2-weighted images that do not 
follow the previous definitions. With aging, the preva- 
lence of all these lesions increases, however, in this sec- 
tion, the latter group is discussed. They will be referred 
to as white matter hyperintensities (WMH). 




52 



M.A. van Buchem 



In most studies, WMH are subdivided in periventrieu- 
lar WMH and subeortieal WMH. Postulated eauses for 
WMH are subependymal gliosis and atrophie perivaseu- 
lar demyelination. The prevalenee and severity of WMH 
inerease with aging. The reported prevalenee in the el- 
derly varies, and depends among other things on the de- 
finition of WMH that is used. In the Cardiovascular 
Health Study, a prevalence of more than 60% was found 
in a population aged 65 years and older. WMH occur 
more frequently and more extensively in women than in 
men, and more white matter change occurs in black indi- 
viduals than in non-blacks. Furthermore, WMH correlate 
with ventricular size but not with sulcal size, which sug- 
gests that ventricular size reflects white matter atrophy 
rather than cortical gray matter atrophy. Apart from age, 
elevated systolic blood pressure, diabetes mellitus, and 
aortic atherosclerosis have been identified as risk factors 
for WMH. WMH often are found in individuals who 
function normally, however in large populations, im- 
paired cognitive and lower extremity functions are asso- 
ciated with WMH. Periventricular WMH are related to 
late-onset depression, whereas WMH in the deep white 
matter are associated with cognitive decline. 

Abnormal Aging 

Classifying the diseases that are discussed in this section 
is arbitrary. I chose to subdivide the diseases according to 
their most striking radiological feature: atrophy or WMH. 
The diseases that are listed in a given category do not on- 
ly have the feature they are listed under, but may have 
other features too. Furthermore, in each description an ef- 
fort is made to describe the difference with normal aging. 
However, making this difference may often not be possi- 
ble, since changes due to normal aging and those that are 
the consequence of a disease may coexist, and also be- 
cause several neurodegenerative disorders may coexist. 

Atrophy 

Disorders that are characterized by cerebral atrophy are 
often associated with dementia. Imaging serves three pur- 
poses in dementia: (1) provide criteria for the diagnosis, 
(2) stage disease severity in Alzheimer’s disease (AD), 
and (3) monitor disease progression. The diagnostic role 
of imaging in dementia can again be subdivided into: (a) 
ruling out treatable disorders such as subdural hematoma, 
hydrocephalus, or intracranial tumor; and (b) providing 
information that suggests a diagnosis. In the appropriate 
clinical setting, imaging can contribute to the diagnosis 
of AD, frontotemporal dementia, vascular dementia, and 
sporadic and variant forms of Creutzfeldt-Jakob disease. 

Alzheimer Disease 

Alzheimer’s disease (AD) is the most common cause of 
dementia, affecting 60%-90% of the elderly with pro- 



gressive memory loss. Symptoms in AD may occur in pa- 
tients as young as 30-40 years of age. In such cases, AD 
often runs in the family and is based on the transmission 
of an autosomal dominant mutation in the amyloid pre- 
cursor protein gene, the presenilin-1 or -2 gene. However, 
in more than 90% of cases, AD is sporadic and becomes 
symptomatic after age 65 years. Histologic findings in 
AD are diffuse cerebral atrophy, particularly affecting the 
gray matter, decreased synaptic density, neuron loss, and 
the presence of neuritic plaques and neurofibrillary tan- 
gles in the cortex. These changes begin in the transen- 
torhinal area and spread gradually via the hippocampus, 
limbic areas in the medial temporal lobe, neocortical as- 
sociation areas to primary sensory and motor areas. On 
cross-sectional imaging, AD is characterized by supra- 
tentorial atrophy. Atrophy occurs diffusely, but particu- 
larly affects the temporal lobes. Manifestations of diffuse 
atrophy are enlarged sulci and widened lateral and third 
ventricles. In the temporal lobe, atrophy affects the en- 
torhinal cortex and hippocampus in particular, and this is 
apparent on cross-sectional images as widening of the 
temporal horn of the lateral ventricle, the choroidal-hip- 
pocampal fissure, suprasellar cistern, and sylvian fissure. 
This may occur symmetrically, asymmetrically, or focal- 
ly. Hippocampal and entorhinal atrophy is best defined 
on coronal images. WMH are frequently found in AD pa- 
tients. However, in the absence of cardiovascular risk fac- 
tors, WMH are not significantly more frequent in AD pa- 
tients compared to normally aging individuals. 

Although AD patients share several characteristics 
with normally aging individuals, on cross-sectional imag- 
ing there are several differences. As compared to normal 
elderly, general cerebral atrophy occurs earlier and in- 
creases faster in AD patients, and significantly more at- 
rophy occurs in the entorhinal cortex and hippocampus. 

Pick^s Disease 

Pick’s disease is a much less common cause of dementia. 
Contrary to AD patients, memory functions are initially 
spared in patients with Pick’s disease. However, these pa- 
tients have prominent behavioral and personality 
changes. The age at onset is similar to that of AD. 
Histologically, Pick’s disease is characterized by neuronal 
swelling, neuronal loss, atrophy and gliosis in the cortex 
and subcortical white matter. On cross-sectional imaging, 
the most striking characteristic of Pick’s disease is severe 
focal atrophy, apparent as widened sulci with shriveled, 
sharp gyri and widening of the lateral ventricles. This 
characteristically occurs in the inferior frontal and anteri- 
or temporal lobes and in the frontoparietal region. These 
atrophic areas contrast sharply with the relatively normal 
posterior temporal lobe, occipital lobes, pre- and post- 
central gyri, and parietal lobes. The left hemisphere is 
more frequently involved than the right. Atrophy may al- 
so be found in the caudate nucleus. On T2-weighted im- 
ages, increased signal intensity may be found in the cor- 
tex and subcortical white matter of the affected areas. 




Brain Degeneration and Aging 

Parkinson Disease 

Clinically, idiopathic Parkinson’s disease is characterized 
by the presence of tremor, rigidity, akinesia, and postural 
difficulties. Parkinson’s disease may coexist with AD. 
The histological hallmark of the disease is loss of 
dopaminergic cells and gliosis in the pars compacta of the 
substantia nigra. On cross-sectional imaging, Parkinson’s 
disease is characterized by non-specific supratentorial at- 
rophy, apparent as widening of sulci and ventricles. More 
subtle and specific changes that may occur in Parkinson’s 
disease are: diminished width of the pars compacta, hy- 
perintense foci on T2-weighted images in the substantia 
nigra, and an increase of the signal intensity of the dor- 
sal lateral substantia nigra (which normally is hy- 
pointense on T2-weighted images) to isointensity to brain 
parenchyma without iron. 

Huntington ^s Disease 

Huntington’s disease (HD) is an autosomal dominant dis- 
order that gives rise to the clinical picture of choreoa- 
thetosis, rigidity, and dementia. The disease is expressed 
in young adulthood. Histologically, HD is characterized 
by neuronal loss, demyelination, gliosis, and iron accu- 
mulation in the striatum. On cross-sectional imaging, the 
most striking feature of HD is atrophy of the caudate nu- 
cleus and putamen. This is apparent as the loss of the usu- 
al bulge of the inferolateral borders of the frontal horns 
of the lateral ventricles. Coexisting abnormalities may be 
diffuse cerebral atrophy, and hyper- and hypointensity of 
the striatum on T2-weighted images. 

Normal Pressure Hydrocephalus 

Normal pressure hydrocephalus (NPH) is clinically char- 
acterized by a triad of gait apraxia, dementia, and urinary 
incontinence. NPH is uncommon under the age of 60 
years, and increases in frequency thereafter. The etiology 
of NPH remains unclear. It has been suggested that inad- 
equate absorption of CSF underlies the disease, but the 
hypothesis has also been put forward that NPH results 
primarily from periventricular white matter damage. 
Whatever the cause is, in a number of patients with NPH 
the clinical symptoms reverse with shunting, whereas the 
symptoms would progress without shunting. Since de- 
mentia is a horrible disorder, and since NPH is one of the 
few treatable causes of dementia, it is important to assess 
on brain scans of every single elderly patient whether 
NPH could be the underlying disease. 

Making the diagnosis of NPH on cross-sectional im- 
ages is a challenge. The most striking characteristic of 
NPH is atrophy. In these patients, both ventricles and 
sulci are widened. However, typically, there is a discrep- 
ancy in the amount of widening of the ventricles and that 
of the sulci, in that the ventricles are wider than would 
be expected from the caliber of the sulci if both phe- 
nomena would just be the consequence of general atro- 



53 

phy. In other words, dilatation of the ventricles is more 
striking than widening of the sulci. On sagittal MR im- 
ages, uniform, smooth thinning and elevation of the cor- 
pus callosum and dilatation of the optic and infundibu- 
lar recesses are apparent. Furthermore, there often is a 
smooth periventricular area of increased signal intensity 
on T2-weighted images, presumably due to increased 
transependymal migration of CSF. Lastly, a pronounced 
flow void may be seen in the aqueduct, due to increased 
CSF hydrodynamics. 

White Matter Hyperintensities 

Vascular Dementia 

Vascular disease may be the cause of dementia in sever- 
al ways. It may be due to multiple large vessel infarcts, a 
single “strategic” infarct, lacunar disease in the basal 
ganglia, and diffuse white matter disease, or leukoaraio- 
sis. 

Whether leukoaraiosis and Binswanger’s disease (BD) 
are the same thing, and whether BD is a symptom or a 
disease, are still matters of debate. BD refers to a condi- 
tion characterized by the presence of abnormalities of the 
white matter on cross-sectional imaging. These areas are 
hypodense on CT, have increased signal intensity on T2- 
weighted images, and sometimes have decreased signal 
intensity on T1 -weighted images. Typically, these areas 
start in the periventricular white matter, and they may 
spread to the surface of the brain, with sparing of the sub- 
cortical U-fibers and cortex. This condition may be asso- 
ciated with widening of the ventricles and with the pres- 
ence of lacunar disease. Histologically, incomplete in- 
farction is found in the abnormal periventricular white 
matter areas. It has been suggested that BD is a small ves- 
sel disease. BD is found in asymptomatic individuals 
over 60 years of age as well as in cognitively impaired pa- 
tients. Still, the extent of the lesions is associated with 
cognitive decline and gait problems. BD probably shares 
its pathogenesis with the periventricular changes that oc- 
cur in normal aging. On cross-sectional images, BD dif- 
fers from normal aging only by the extent of the white 
matter abnormalities. 

Suggested Reading 

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the brain: prevalence and anatomic characteristics at MR 
imaging of the elderly - data from the Cardiovascular Health 
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Caplan LR (1995) Binswanger’s disease - revisited. Neurology 
45:626-633 

Drayer BP (1988) Imaging of the aging brain. Part I. Normal find- 
ings. Radiology 166:785-796 

Drayer BP (1988) Imaging of the aging brain. Part II. Pathologic 
conditions. Radiology 166:797-806 




54 



M.A. van Buchem 



Esiri MM, Hyman BT, Beyreuther K, Masters CL (1997) Ageing 
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of physiological cerebral atrophy with aging: a statistical 
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matter abnormalities 100 years after Binswanger’s report - a 
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Roman GC (1996) From UBOs to Binswanger’s disease - impact 
of MRJ on vascular dementia research. Stroke 27:1269-1273 
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the NINDS-AIREN International Workshop. Neurology 
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IDKD 2004 



Imaging the Effects of Systemic Metabolic Diseases on the Brain 

M. Castillo 

Department of Neuroradiology, University of North Carolina, Chapel Hill, NC, USA 



Introduction 

Brain function depends on a consistent supply of oxygen 
and glucose. Many systemic disorders that interfere with 
the metabolism of these two substances result in neuro- 
logical dysfunction. The brain is commonly affected by 
disorders primarily involving the heart, liver, kidneys, 
blood, and endocrine organs. Most cardiac disorders re- 
sult in ischemic brain damage and are not addressed here. 
The most common liver disorders to affect the brain are 
those resulting in acute and chronic hepatic failure. The 
central nervous system (CNS) is also affected by disor- 
ders of the metabolism of elemental substances such as 
salts and metals. The most common disorders in this cat- 
egory involve those related to copper, sodium, and iron 
metabolism. CNS injiuies may also result from extrane- 
ous substances, either toxic or those used as medications. 
Substances toxic to the CNS include carbon monoxide, 
glycol, lead, methanol, mercury, and toluene. In this pa- 
per, I also address miscellaneous disorders including hy- 
poglycemia, anorexia nervosa, chronic fatigue syndrome, 
porphyria and amyloidosis and their effects on the CNS. 
CNS disorders may also be associated with gastrointesti- 
nal disorders. 



Liver Failure and Parenteral Nutrition 

Hepatic insufficiency leads to abnormalities on magnetic 
resonance imaging (MRI) of the brain. T1 -weighted im- 
ages show increased signal in the caudate nucleus, tectum 
(particularly the inferior colliculi), globus pallidus, puta- 
men, subthalamic nucleus, red nucleus, adenohypoph- 
ysis, and substantia nigra. Abnormalities are bilateral, 
symmetrical, and of homogenous signal intensity. There 
no corresponding abnormalities on T2-weighted images, 
and computed tomography (CT) results are normal. MRI 
findings are due to increased amounts of manganese 
(Mn) and other factors leading to shortening of relaxation 
time. Increased plasma levels of Mn are found in patients 
with chronic liver failure and occupational toxicity, and 
in those receiving long-term parenteral nutrition. 



Approximately 95% of Mn is excreted in bile. Mn is in- 
volved in enzymatic cycles involving superoxide dismu- 
tase and glutamine synthetase. Mn reaches the brain by 
way of erythrocytes and plasma. Transferrin and albumin 
are its carriers in plasma. The half-life of blood Mn is 10- 
42 days but when it reaches the brain it may remain there 
for prolonged periods of time. Astrocytes have specific 
transport systems for Mn. Mn is neurotoxic and results in 
striatal dopamine depletion, NMDA excitotoxicity, and 
oxidative stress. Mn plays a role in development of he- 
patic encephalopathy, clinically characterized by pyrami- 
dal and extrapyramidal dysfunctions, brisk tendon reflex- 
es, and tremors. The concentration of Mn in the pallidus 
of cirrhotic patients is 3-fold higher compared to con- 
trols. The frequency of MRI abnormalities in cirrhotic 
patients is about 73%. 

Alper’s S 5 mdrome is a rare childhood disorder charac- 
terized by progressive neuronal degeneration with liver 
disease. These patients develop seizures and liver failure. 
There is necrosis of deep gray nuclei and cortex. MRI 
shows high T2 signal in basal ganglia and thalamus. 
There is atrophy and high T2 signal in the cortex, pre- 
dominantly occipital. The abnormalities are bilateral and 
asymmetrical. The abnormalities may reflect mitochon- 
drial dysfunction. 

Long-term total parenteral nutrition results in high T1 
signal in the same regions. These solutions are rich in 
Mn and produce neurological symptoms. Once the par- 
enteral nutrition is discontinued, the MRI abnormalities 
reverse to normal. The amount of time required for these 
abnormalities to resolve is not clear but most do one year 
after cessation of parenteral nutrition. In one case, T1 
hyperintensity developed in the adenohypophysis and 
dorsal brain stem 3 months after total parenteral nutri- 
tion and reverted to normal 4 months after treatment. 
Similar findings have been noted in patients following 
liver transplantation. Although the clinical and imaging 
abnormalities are reversible in adults, its effects on the 
child’s brain are not known. Repeated episodes of hepat- 
ic failure lead to the development of acquired (non- 
wilsonian) hepatocerebral degeneration. The clinical 
symptoms are permanent and death follows. By MRI, 




56 



M. Castillo 



these patients do not show T1 hyperintensities in basal 
ganglia as described previously for chronic hepatic en- 
cephalopathy. Patients with acquired hepatocerebral de- 
generation show high T2 signal in the middle cerebral 
peduncles. These zones correspond to spongiform myeli- 
nolytic changes. 

Bilirubin Encephalopathy 

Kernicterus is now a rare disorder. Most cases result 
from isoimmunization to Rh factor or from ABO blood 
group incompatibility. It is almost always a disease of 
neonates. Later in life, most cases are due to genetic 
hematologic or liver diseases (e.g. defects of glucose-6- 
phosphate dehydrogenase, Crigler-Najjar disease, 
Gilbert's disease) or are secondary to breast-feeding or 
severe sepsis. In kernicterus, the liver is unable to con- 
jugate bilirubin. The enzyme uridine-diphosphate glu- 
coronyl transferase does not function well and albumin- 
bound (insoluble) bilirubin cannot be deconjugated into 
bilirubin diglucoronide or “water soluble” bilirubin. 
Initially there is hypotonia, then hypertonia and after 
one week, hypotonia returns. There is yellow staining of 
the globi pallidi, mamillary bodies, subthalamic nuclei, 
and indusium griseum. In the brain stem, the substantia 
nigra and cranial nerve nuclei are involved. In the 
chronic stage, there is high T2 signal in the globi palli- 
di and cerebellar dentate nuclei. These structures are at- 
rophic. Acutely, there is high T1 signal in basal ganglia 
without corresponding abnormalities on T2-weighted 
images. This finding is probably related to acute hepat- 
ic insufficiency. 

Wilson’s Disease 

Wilson’s disease (WD) is a genetic disorder of copper 
metabolism characterized by failure to incorporate cop- 
per into ceruloplasmin in the liver, failure to excrete 
copper by the liver into bile, and accumulation of cop- 
per. Its defect is mapped to chromosome 13. Most chil- 
dren present with hepatic failure and adults present with 
neurological symptoms. Accumulation of copper within 
Descemet’s membrane results in Kayser-Fleischer rings. 
Copper in the lens results in “sunflower” cataracts. 
There is cell loss and cavitation in the lentiform nucle- 
us. Other regions involved include thalami, subthalami, 
red nuclei, substantia nigra, dentate nuclei and brain 
stem. These regions contain large cells with small nuclei 
(termed Opalski cells) which are typical of WD. MRI 
shows abnormalities even in absence of symptoms. 
Paramagnetic effects of copper are visible by MRI in 
untreated patients. Basal ganglia lesions are bilateral 
and symmetrical. The putamina show high T2 signal. 
Thalamic involvement spares the dorsomedial nuclei. 
The dentatothalamic, corticospinal and pontocerebellar 
tracts are involved. The claustrum shows high T2 signal. 



The midbrain is T2 bright with relative sparing of its 
deep nuclei (Panda sign). The high copper concentra- 
tions are not responsible for the MRI findings. Copper 
results in T1 and T2 shortening, thus the MRI findings 
are probably due to spongy degeneration, cavitation, 
neuronal loss and gliosis. The abnormal striatum corre- 
lates with pseudoparkinsonism, an abnormal denta- 
tothalamic tract with cerebellar signs and an abnormal 
pontocerebellar tract with pseudoparkinsonism. The 
presence of portosystemic shunting correlates with ab- 
normalities seen in the globi pallidi. The abnormal T2 
signal improves after copper-trapping therapy. Contrast 
enhancement is rare but may be seen when patients re- 
ceive treatment with penicillamine. 

Carbon Monoxide 

Carbon monoxide (CO) results in nearly 6000 accidental 
and suicidal deaths in the US. Common causes of high 
CO levels are burning of gasoline, kerosene, wood, coal 
and propane. Individuals working in enclosed spaces are 
prone to acute CO intoxication (“warehouse workers 
headache”). Hemoglobin has 200- to 250-times more 
affinity for CO than for carbon dioxide. CO affects the 
cytochrome oxidase system, impairs release of oxygen in 
tissues and results in lipid peroxidation. Symptoms oc- 
cur early, but their severity has no correlation with blood 
levels of CO. Early symptoms include headache, im- 
paired vigilance and abnormal audition and vision. 
Severe symptoms are nausea, vomiting, seizures, syn- 
cope, coma and death. Classic findings, such as “cherry 
red” mucosa, are rare. 

CO has two effects in the brain. First, it binds to re- 
gions having high oxygen demand such as the globi pal- 
lidi. Second, CO binds to normal iron-containing struc- 
tures such as the substantia nigra. Systemic hypotension 
contributes to brain lesions. MRI and CT show lesions 
mostly in the globi pallidi. The lesions are of low densi- 
ty and high T2 signal and contain no hemorrhage. 

Glycol-related Products 

Ethylene glycol found in automobile antifreeze, hy- 
draulic fluid and industrial solvents is a common cause 
of poisoning and suicide. Diethylene glycol and propy- 
lene glycol are also toxic and are used to contaminate 
medications such as acetaminophen. After the ingestion 
of ethylene glycol, metabolic acidosis ensues and results 
in kidney damage due to accumulation of calcium and 
oxalate crystals in urine. Blindness is typical of ethylene 
glycol poisoning. MRI shows high T2 signal in the put- 
amina, globi pallidi, caudate nuclei and thalami. 
Symptoms of intoxication with diethylene glycol and 
propylene glycol include fever, vomiting, diarrhea, 
cough, abdominal pain, altered mentation, dyspnea and 
acute renal failure. 




Imaging the Effects of Systemic Metabolic Diseases on the Brain 

Lead 

Acute lead (Pb) poisoning is rare. Most lead poisoning 
occurs in children due to ingestion of peeling paint 
chips. Since 1978, lead-based paint has not been used in 
the United States. Acute lead poisoning results in en- 
cephalopathy and cerebral edema. Gross examination of 
the brain shows congestion, petechial hemorrhages, 
thrombosis and demyelination. In adults, most lead poi- 
soning is chronic. Chronic lead intoxication is a conse- 
quence of gasoline sniffing, inhalation of automobile ex- 
haust fumes, lead smelting, consumption of “moon- 
shine” whiskey, battery manufacturing and lead glazing 
of pottery. Chronic exposure to lead results in intracra- 
nial calcifications particularly in the cerebellum. These 
calcifications are dystrophic and due to vascular dam- 
age. CT shows widening of cranial sutures in cases of 
chronic lead poisoning and hypodensity in the subinsu- 
lar regions, or may be normal. 

Methanol 

Methanol (methyl alcohol) is used for production of an- 
tifreeze solution, illegal drinks and poor-quality 
cologne. After ingestion of methanol, there is a latent 
period varying from 1 to 72 hours. Thereafter, metabol- 
ic acidosis and cortical blindness ensue. Other symp- 
toms are parkinsonism, inebriation, headache, dizziness, 
seizures and coma. Methanol and its byproducts 
(formaldehyde and formic acid) are toxic to the CNS. 
Putaminal hemorrhagic necrosis is typical. The putami- 
na are swollen, of low density, and contain small hem- 
orrhages. MRI shows these regions to have either low or 
high T1 signal and hyperintensity on T2-weighted im- 
ages. Other patients also show cortical necrosis particu- 
larly in the paramedian frontal lobes reflected by high 
T2 signal. Optic atrophy is seen but the signal in these 
structures remains normal. The white matter may be 
edematous. 



Mercury 

Mercury (Hg) poisoning is rare and occurs after the in- 
gestion of organic or inorganic mercury. Organic mer- 
cury intoxication results from eating contaminated fish 
or pork (due to used of Hg-based fungicides). 
Symptoms include ataxia, neuropathy, choreoathetosis, 
visual loss, confusion and coma. Chronic ingestion of 
Hg-laden fish, first described in Japan (Minamata dis- 
ease), is now being found in other parts of the world. 
MRI shows atrophy of the calcarine and post-central 
cortices and cerebellar vermis. These areas are slight- 
ly hypointense on T1 -weighted images and of high T2 
signal. These findings reflect spongiosis and are cor- 
related with visual field deficits, sensory abnormali- 
ties and ataxia. 



57 

Inhalant Abuse 

Inhaling solvents, volatile substances and glue vapors in- 
duces a transient euphoric state. Inhalant abuse occurs in 
teenagers. Fumes are inhaled directly or by placing the 
substance in a bag or on a rag. After an initial euphoric 
state, drowsiness and sleep ensue. These compounds have 
a great affinity for the lipid-laden brain. Suffocation, as- 
piration and dangerous behavior are causes of death in 
subjects who use inhalants. 

Chronic abuse of toluene results in cognitive impair- 
ment, cerebellar ataxia, tremor, and anosmia. MRI shows 
cerebral, cerebellar and brain stem atrophy. T2-weighted 
images show abnormal high signal in white matter due to 
gliosis. Hypointensity in basal ganglia and thalami is the 
result of iron deposition. Other MRI findings in toluene 
abuse are loss of cerebral and cerebellar gray-white mat- 
ter discrimination, scattered foci of abnormal signal in 
white matter, a thin corpus callosum and atrophy. 

Disorders of Ethanol Abuse 

Chronic alcohol consumption results in ataxia and lower 
limb inco-ordination due to cerebellar atrophy. 
Cerebellar atrophy is present in over 60% of alcoholics. 
There is shrinkage of folia particularly in the superior 
vermis reflecting loss of Purkinje cells. Alcoholic 
myelopathy and peripheral neuropathy are related to de- 
ficiency of thiamine. Acute symptoms of Wernicke- 
Korsakoff (WK) syndrome include lethargy, confusion, 
altered memory, nystagmus, ophthalmoplegia and atax- 
ia. WK syndrome is mostly seen in alcoholics but may 
be due to anorexia, protracted vomiting, digitalis toxici- 
ty, gastric plication, starvation and acquired immune de- 
ficiency syndrome (AIDS). 

A common underlying factor in all these conditions is 
thiamine (vitamin Bl) deficiency. B1 metabolism plays 
roles in brain glucose oxidation and membrane perme- 
ability. After treatment, patients develop chronic memo- 
ry problems (Korsakoff’s psychosis). Glutamate is found 
in high concentrations in Bl -depleted brains. Cerebral 
lactic acidosis occurs early. Acutely there is vascular di- 
latation and endothelial swelling involving small arteries 
followed by neuronal damage and astrocytoma swelling. 
This leads to ischemia of the mamillary bodies, the dor- 
somedial thalamic nuclei, pulvinars, walls of the third 
ventricle, periaqueductal gray matter, colliculi, third cra- 
nial nerve nuclei, inferior olives and superior cerebellar 
vermis. On T2-weighted images, these regions show 
high signal intensity. Contrast enhancement of the 
mamillary bodies is pathognomonic of this condition. 
Hemorrhage is found in 20% of cases. In chronic stages, 
there is brain atrophy more prominent in the fornices and 
mamillary bodies. 

Marchiafava-Bignami (MB) disease is seen mostly in 
chronic alcoholics. It was initially described in drinkers 
of Italian red wine but may be seen in persons ingesting 




58 



M. Castillo 



other types of alcoholic beverages. There is cystic necro- 
sis of the corpus callosum, particularly the genu and 
body. Similar lesions are seen in the optic chiasm, ante- 
rior commissure, centrum semiovale and brachium pon- 
tis. There is demyelination with axonal preservation. MRI 
shows the anterior corpus callosum to be of low T1 sig- 
nal and high T2 signal. Areas of high T2 signal are also 
seen in the centrum semiovale. 

Alcohol is most common teratogenic agent to which 
human beings are exposed. The fetal-alcohol syndrome 
(FAS) was first described in the United States and in 
France but is now prevalent in other countries such as 
Russia. It is clinically characterized by mental retarda- 
tion, anomalies of the CNS, dysmorphic facial features, 
and skeletal, cardiac, and urogenital abnormalities. 
Unfortunately, the mental deficits are permanent and do 
not improve with age. The most common brain abnor- 
malities observed in FAS are microcephaly, dysgenesis 
(and agenesis) of the corpus callosum, dysgenesis of the 
cerebellum and the brain stem, occipital meningoen- 
cephalocele, myelomeningocele, and holoprosencephaly. 
Facial anomalies include thin lips, small mandible and 
maxilla, and cleft lip and palate. Alcohol or its metabo- 
lites have adverse effects in the gastrulation stage of em- 
bryonic development by causing a reduction in the num- 
ber of cells in the early neural plate and increased cell 
death (apoptosis) at the margins of the anterior neural 
folds. This mechanism explains the coexistence of brain 
and facial anomalies in FAS. Other common teratogens 
include carbamazepine, valproic acid, retinoin, pheny- 
toin, toluene, trimethadione, warfarin, cocaine, and prob- 
ably benzodiazepine. 

Sodium (Na) imbalance results in a diffuse injury (hy- 
ponatremic encephalopathy) or focal lesions (osmotic 
myelinolysis). Hyponatremia results Irom excess water 
and urinary loss of Na cations. Abnormal secretion of 
antidiuretic hormone (ADH) results in hypervolemia. 
When plasma osmolality falls, cellular equilibrium is 
maintained by excretion of intracellular solutes and dilu- 
tion of the intracellular compartment by influx of water 
into cells. Cellular damage occurs as a consequence of 
water influx. In acute hyponatremic encephalopathy, 
death results from swelling and herniation. Most patients 
with hyponatremic encephalopathy have one or more of 
the following conditions: postoperative state, polydipsia- 
hyponatremia syndrome, congestive heart failure and 
AIDS. In addition to damage induced by low Na, most 
patients are hypoxic. 

A common demyelinating lesion associated with cor- 
rection of hyponatremia is central pontine myelinolysis 
(CPM). Conditions leading to CPM are alcoholism, ex- 
tensive burns, sepsis, Hodgkin's disease and other tu- 
mors. Myelinolysis is not the sequela of hyponatremia 
but is secondary to its correction. Rapid correction of 
hyponatremia increases the risk of developing myelinol- 
ysis. CPM ensues 2-3 days after a hyponatremic event. 
Over 85% of patients suspected to have CPM show no 
imaging abnormalities. Microscopically, CPM consists 



in destruction of myelin and relative preservation of ax- 
ons. The lesion is symmetrical and located in basis pon- 
tis. The cerebellar cortex is also affected. About 10% of 
patients with CPM have other lesions, mostly supraten- 
torial. Myelinolysis often involves the deep gray struc- 
tures. The thalamus is affected but the cortex and sub- 
cortical regions may also be involved. CPM has low T1 
signal and high T2 signal. On axial views, the lesion is 
round or triangular. On coronal views, it has a “Batman” 
sign configuration. Contrast enhancement is rare. 
Prognosis is variable: some patients die while others sur- 
vive. Survivors may improve slowly or not at all. 

Hallervorden-Spatz Disease 

This disease is related to iron (Fe) overload and degener- 
ation. Little is known about the biochemical abnormali- 
ties of Hallervorden-Spatz (HS) disease, although it is 
linked to an abnormality on chromosome 20pl2.3-pl3. 
Iron is deposited in the globi pallidi and pars reticulata of 
the substantia nigra. Iron deposition leads to axonal 
swelling and decreased myelin content and production. 
Microscopy demonstrates abnormal, spherical bodies 
containing superoxide dismutase. Eventually, these re- 
gions are destroyed. Patients demonstrate dystonia, mus- 
cle rigidity, hyperreflexia and choreoathetosis. Mental re- 
tardation is variable and death occurs 1-2 years after di- 
agnosis. Initially, MRI shows T2 hypointensity in the glo- 
bi pallidi. When gliosis ensues, the globi pallidi become 
bright on T2-weighted images and surrounded by hy- 
pointensity. This is the “eye of the tiger” sign. 

Hypoglycemia and Hyperglycemia 

Most cerebral insults due to hypoglycemia occur in 
young children. Oxygen and glucose are major sub- 
strates needed for normal brain metabolism, and absence 
of either leads to significant injury. The neonatal brain is 
fairly resistant to hypoglycemia. Acute symptoms of hy- 
poglycemia are jitteriness, seizures and vomiting. 
Hypoglycemia is diagnosed when whole blood glucose 
concentration falls below 20 mg/dl in preterm babies, 30 
mg/dl in term babies and 45 mg/dl in adults. Sequelae of 
hypoglycemia are mental retardation, spastieity, visual 
abnormalities and microcephaly. In neonates, hypo- 
glycemia leads to edema and infarctions. The occipital 
regions are affected more severely but the basal ganglia 
are also involved. Chronically, the occipital cortex be- 
comes thin, malacia develops and these findings corre- 
late with visual abnormalities. In adults, hypoglycemia 
also induces oecipital infarctions in addition to infarc- 
tions elsewhere (which are generally multiple) and lam- 
inar necrosis. 

Hyperglycemia may increase cerebral lactic acid and 
damage the brain primarily or worsen the outcome of pa- 
tients with underlying infarctions. A typical manifesta- 




Imaging the Effects of Systemic Metabolic Diseases on the Brain 



59 



tion is hemichorea-hemiballismus (HH). Symptoms of 
HH are random and fast jerking motions in the distal ex- 
tremities (chorea) and violent flinging and kicking main- 
ly in the proximal joints (ballismus). CT shows high den- 
sity in one lentiform nucleus and head of the ipsilateral 



caudate nucleus. These regions are of high T1 signal 
while T2-weighted images are normal. Occasionally, the 
ipsilateral cerebral peduncle may show T1 hyperintensity 
in its anteromedial region. Findings are thought to be due 
to the presence of gemistocytes. 




IDKD 2004 



Neuroradiological Diagnosis of Craniocerebral and Spinal Trauma: 
Current Concepts 

P.M. ParizeP, C.D. Phillips^ 

^ Department of Radiology, University of Antwerp, Antwerp, Belgium 
^ Department of Radiology, University of Virginia Health System, Charlottesville, VA, USA 



Imaging Techniques 

Traditionally, X-ray films of the skull have been used to 
detect skull fractures, intracranial mass effect (“pineal 
shift”), air-fluid levels and foreign objects (e.g. metal, 
glass, projectile fragments). However, the diagnostic 
yield of plain X-ray films is low because there is poor 
correlation between skull fractures and intracranial in- 
jury. When computed tomography is available, plain skull 
films contribute little or no additional information in the 
clinical management of the acute trauma patient. 

Computed tomography (CT) is the initial imaging 
study of choice in acute craniocerebral trauma. It is a 
rapid and accurate technique. The availability of CT has 
dramatically improved the survival of patients with 
epidural and subdural hematomas. Critically injured pa- 
tients can be monitored within the scanner with relative 
ease. CT is used for the detection of: 

- Hemorrhage (intra-axial and extra-axial, including 
subarachnoid blood), 

- Mass effect, edema and brain herniations, 

- Fractures and displaced bone fragments (using bone 
window settings), and 

- Foreign bodies. 

The CT examination should start with a lateral scout 
image, which can be used as a digital radiograph to de- 
tect fractures. The non-contrast scan is performed with 
contiguous axial sections (slice thickness, 5 mm) from 
the base of the skull to the vertex; alternatively, a spiral 
technique can be used. CT images of the head should be 
obtained using 3 window settings: 

- Brain parenchyma window (level, 40 HU; width, 80- 
120 HU); 

- Bone window (level, 500 HU; width, 2000-4000 HU); 
recalculation of raw image data with a bone or edge al- 
gorithm is useful; 

- Subdural window (level, 70-100 HU; width, 150-300 
HU) for the detection of a thin layer of blood against 
the dense calvarium. 

If the patient is clinically unstable or rapidly deteriorat- 
ing, the CT procedure needs to be foreshortened (e.g. sin- 



gle mid-ventricular image). When fractures of the tempo- 
ral bone, orbit, or maxillofacial structures are suspected, 
additional thin slices in different orientations should be 
obtained. Spiral CT with coronal reformatting can be used 
as an alternative to direct coronal views when the patient 
cannot tolerate hyperextension of the neck. Multidetector 
CT (MDCT) is now used in major trauma centers for rapid 
screening of the skull, spine, and their contents. The MD- 
CT data set can be used for high-resolution three-dimen- 
sional (3D) surface reconstructions (Fig. 1). 

Magnetic resonance imaging (MRI) is the preferred tech- 
nique in the evaluation of subacute and chronic brain injury. 
MRI has the highest sensitivity for parenchymal lesion de- 
tection, and is especially useful in evaluating lesions in the 




Fig. 1. Depressed skull fracture. Surface shaded display (SSD), 
obtained from a 3D multidetector CT data set, reveals the irregu- 
lar, jagged edges of a right frontal depressed skull fracture 





Neuroradiological Diagnosis of Craniocerebral and Spinal Trauma: Current Concepts 



61 



posterior fossa or near the skull base (difficult to see on CT 
due to beam hardening artifacts), diffuse axonal injury due 
to shearing stresses, and cortical contusions. Important lim- 
itations include the relative insensitivity for the detection of 
subarachnoid hemorrhage, cortical bone injury and small 
bone fragments. Our standard imaging protocol consists of: 

1. Axial fast spin echo (FSE) T2-weighted imaging; 

2. Axial fluid attenuated inversion recovery (FLAIR) T2- 
weighted imaging for the detection of gliosis and en- 
cephalomalacia; 

3. Axial or coronal gradient echo fast low angle shot 
(FLASH) imaging with dual echo times (TL, 15 and 
35 ms) for the detection of hemorrhagic foci (e.g. in 
diffuse axonal injury); 

4. Sagittal spin echo (SL) or gradient echo T1 -weighted 
imaging for the detection of cortical contusions or 
post-traumatic encephalomalacia in the anterior and 
inferior parts of the frontal lobes, and in the anterior 
temporal lobes; 

5. Diffusion- weighted echo planar imaging (LPI) in the 
acute phase. 

Scalp and Skull Lesions 

Scalp and skull lesions are commonly observed in head trau- 
ma. Scalp lacerations occur when the scalp is crushed and 
split against the underlying bone. These lesions heal well be- 
cause of the generous blood supply (this also explains why 
scalp wounds bleed profusely). Scalp wounds must be care- 
fully examined to exclude foreign bodies or depressed bone 
fragments. CT is the preferred imaging technique for show- 
ing soft tissue swelling of the scalp. When the integrity of 
the skin is disrupted, a scalp hematoma may contain small 
amounts of air. CT shows not only the scalp lesions, but al- 
so the associated osseous and intracranial abnormalities. 
Multidetector CT allows rapid visualization of the entire cra- 
nium, with 3D rendering of the skull bones (Fig. 1). 

Caput succedaneum, subgaleal hematoma, subgaleal 
hygroma, and cephalohematoma are commonly confused 
(Fig. 2). Table I provides a comparative summary of the 
distinct features of these entities. 



Maxillofacial Injuries 

Maxillofacial injuries are not uncommon accompaniments 
to central nervous system (CNS) trauma. The facial skele- 
ton is commonly injured during head trauma. Head trauma 
may result in intracranial injuries which are often the crit- 
ical injuries in the immediate trauma setting. However, ma- 
jor facial trauma may be a serious cause of morbidity and 
mortality. Respiratory problems may accompany major fa- 
cial trauma. Major morbidity in this patient group may re- 
sult from facial injuries in the subacute period. The injuries 
which lead to considerable patient morbidity include: or- 
bital trauma; central skull base and temporal bone frac- 
tures, with resulting injury to a number of cranial nerves. 



vascular structures and adjacent soft tissue structures; and 
obvious deformity and loss of function. 

The era of fast CT with multidetector units has led to a 
significant alteration in the acute imaging of patients with 
maxillofacial injuries. Quite simply, the rapidity of CT - 
with thin sections and multiplanar reconstruction (MPR) 




Fig. 2a, b. Hemorrhagic cerebral contusions and subgaleal 
hematoma in a 13 -year-old boy injured in a motor vehicle acci- 
dent. a Sagittal SE T1 -weighted image, b Axial TSE T2-weighted 
image. Intracranially, there are hemorrhagic cerebral contusions in 
the right frontal and anterior temporal lobes. Extracranially, there 
is marked bilateral swelling of the subcutaneous soft tissues due to 
a massive subgaleal hematoma which extends from the frontal to 
the posterior parietal region 





62 



RM. Parizel, C.D. Phillips 



Table 1. Overview of scalp lesions 





Caput 

succedaneum 


Subgaleal 

hematoma^ 


Subgaleal 

hygroma 


Cephalohematoma^ 


Occurrence 


Normal vaginal 
delivery 


Head trauma 
(or after birth) 


Birth trauma 
(forceps delivery) 


Birth trauma (skull 
fracture during birth) 


Location 


Above of the galea 
aponeurotica 


Beneath the galea 
aponeurotica 


Beneath the galea 
aponeurotica 


Subperiosteal (flat 
flat skull skull bones) 


Composition 


Edema (with with 
microscopic hemorrhages) 


Venous blood 


Cerebrospinal fluid 


Subperiosteal 

hemorrhage 


Clinical 

presentation 


Pitting edema 


Diftusely spreading, 
firm, fluctuating mass 


Fluctuating collection 


Well defined, focal, 
firm mass 


Skull fracture 


No • 


Yes or no 


Yes 


Yes 


Crosses suture lines? 


Yes 


Yes 


Yes 


No 



^ Extracranial subdural hematoma 
^ Extracranial epidural hematoma 



that rival the quality of directly acquired images in the 
sagittal and coronal planes - has led many services to per- 
form the entire evaluation of a trauma patient (CNS, ab- 
domen, pelvis, spine, and the detailed evaluation of facial 
trauma) in one setting. We have adopted a series of trauma 
protocols for patient evaluation, which simplifies the tech- 
nologists’ plan for imaging in this patient group. The ini- 
tial exam is unenhanced CT of the brain, with the scan 
simply begun at the level of the midface or mandible (de- 
pending on the injuries noted), followed quickly by the re- 
quested trauma abdominal, chest, or pelvic examination as 
required by the trauma service. In the setting of major trau- 
ma, the examination then addresses the cervical spine or 
other affected spinal segments. Cervical spine CT may ac- 
company the initial head and face CT exam. When the pa- 
tient has significant injuries and there is minimal time to 
spend in the CT suite, it is possible to obtain good quality 
examinations of the lumbar or thoracic spine from refor- 
matted data from the abdominal, chest, or pelvic CT study. 

We prefer to initially categorize injuries to the facial 
skeleton by the presence or absence of involvement of the 
pterygoid plates. Fracture of the pterygoid plates results in 
dissociation of the facial skeleton and the slmll. These frac- 
tures were first examined in detail by the French surgeon 
LeFort. His rather gruesome investigation involved blunt 
trauma to the midface of cadavers, with subsequent investi- 
gation of the patterns of fracture. LeFort categorized three 
different levels of fracture, a system still utilized to large ex- 
tent to this day. LeFort I injuries result in a “floating palate”, 
with the fracture plane below the level of the orbital rim, 
which allows mobility of the inferior maxilla in relation to 
the remainder of the midface. LeFort II injuries result in dis- 
sociation of the palate and the inferior orbital rim on the in- 
volved side. The fracture involves the medial and lateral 
maxilla but will permit displacement of the inferior orbital 
rim if traction is applied to the palate. LeFort III fractures re- 
sult in dissociation of the entire midface in relation to the 
skull, and the superior fracture plane involves the root of the 
nasal bone. We have found that axial, coronal, and particu- 
larly sagittal CT images allow excellent assessment of these 



fractures. There are other fairly common patterns of facial 
injury, easily characterized by CT examination. The “tri- 
pod”, or trimalar fracture (Fig. 3) accompanies an angular 




Fig. 3a, b. Tripod fracture, a Axial CT slice through the orbits, 
b Surface shaded display (SSD), obtained from a 3D multidetector 
CT data set. These images reveal the typical features of a left-sided 
tripod injury: there are fractures of the zygomatic arch, the anteri- 
or wall of the maxilla, and the posterolateral wall of the maxilla. 
This type of injury is caused by an angular blow to the midface, 
typically in proximity to the zygomaticomaxillary suture 



Neuroradiological Diagnosis of Craniocerebral and Spinal Trauma: Current Concepts 



63 




Fig. 4a-c. Blow-out fracture of the right orbital floor, a Coronal multidetector CT refor- 
matted image, soft tissue window, b Sagittal multidetector CT reformatted image, bone 
window, c SSD display. The right orbital floor is fractured with displacement of small bone 
fragments and intraorbital fat into the maxillary sinus. The orbital rim is intact (c). The maxillary sinus is partially opacified (hematoma). 
There is orbital emphysema 



blow to the midface, typically in proximity to the zygomati- 
comaxillary suture. The injury results in fractures of the zy- 
gomatic arch, the anterior wall of the maxilla, and the pos- 
terolateral wall of the maxilla. Isolated orbit fractures (Fig. 
4), fractures of the orbital rims, nasal bones, zygomatic arch, 
maxillary and mandibular alveoli, and mandible may be 
seen. There is also wide acceptance of the value of 3D im- 
ages in the review of these injuries. The ease with which 
these exams can be post-processed has led to an increased 
utilization in the acute trauma setting. We now routinely 
produce these images for our trauma service. They likely 
provide little new data, but the ability to see the entirety of 
the injury in few images is useful to surgeons, and of con- 
siderable importance when considering reconstruction. 

Investigation of facial fractures should include careful 
review of the important skull base foramina, and of the 
soft tissue structures of the midface. A careful review of 
the soft tissue windows of the midfacial structures should 
always be performed. Evaluation of the orbital soft tissues 
is critical with injury in this region (Fig. 4). Particular at- 
tention should be paid to the carotid canal and optic canal. 
Involvement of either of these foramina may lead to sur- 
gical management or to additional investigations. 

Temporal bone fraetures are beyond the scope of this re- 
view, but can be divided into longitudinal or transverse frac- 
tures, depending upon the fracture orientation in relation to 
the axis of the temporal bone. Many of these fractures are 
complex, with orientation in both the longitudinal and trans- 
verse planes. Longitudinal fractures are more commonly as- 
sociated with ossicular involvement and hearing loss, and 
transverse fractures are more eommonly associated with fa- 
cial nerve injury. There is eonsiderable overlap, however. 
Previously, with single-slice CT units, questionable involve- 
ment of the skull base led to re-scanning this region with 
thin slices, and with a larger cumulative dose to the patient. 
In the era of MDCT, often the initial data set can be refor- 
matted to permit a thorough evaluation of the temporal bone. 
Whenever the question is raised as to the possibility of tem- 
poral bone fraeture, it is inherent in our responsibility to en- 
sure that the examination is adequate to answer the question. 



Severely injured patients with faeial fractures may un- 
dergo MRI for other injuries, but review of the soft tissues 
of the face is rarely a concern that requires dedicated MRI. 
Injuries of the orbit, notably the question of involvement of 
the optic nerve, may on oceasion necessitate MRI. 

Intracranial Hypertension and Cerebral 
Herniation 

Severe brain swelling or large intracranial mass lesions 
(e.g. hemorrhage) cause displaeement of brain tissue. 
The eranial cavity is divided into anatomie compart- 
ments by combination of bony ridges and dural septa 
(falx cerebri and tentorium cerebelli). The three major 
compartments contain: (I) the right cerebral hemisphere, 
(2) the left cerebral hemisphere, and (3) the posterior 
fossa structures. The falx and the tentorium proteet the 
brain against excessive motion but also limit the amount 
of compensatory shift and displacement that develops in 
response to inereased intracranial pressure (ICP). When 
the pressure in one of the dural compartments inereases 
beyond the physiological compensatory mechanisms, in- 
creased ICP or intracranial hypertension occurs and a 
pressure gradient ensues. This leads to a displacement of 
brain, cerebrospinal fluid (CSF) and blood vessels from 
one cranial compartment to another and a cerebral her- 
niation follows. 

Cerebral herniations are the most common secondary 
effects of an expanding intracranial mass. They can be 
due to an intra-axial proeess (e.g. intracerebral contusion 
or hematoma, edema, tumor) or an extra-axial mass (e.g. 
epidural or subdural hematoma). The subarachnoid 
spaces and basal cisterns become obliterated, hydro- 
cephalus develops, vascular compression results in brain 
ischemia, and compression on vital brain tissue causes 
profound neurological deficits. Therefore, early detection 
of brain herniation can be of major clinical importance in 
patient management. Six types of brain herniation can be 
distinguished (Table 2). 




Table 2. Cerebral herniation types 



64 



P.M. Parizel, C.D. Phillips 



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EDH, epidural hematoma; SDH, subdural hematoma; ICP, intracranial pressure; CPA, cerebellopontine angle; ACA, anterior cerebral artery, PICA, posterior inferior cerebellar artery; 
PC A, posterior cerebral artery; SC A, superior cerebellar artery 




Neuroradiological Diagnosis of Craniocerebral and Spinal Trauma: Current Concepts 

Extra-axial Lesions 



65 



Four types of extra-axial hemorrhage can be considered: 
epidural, subdural, subarachnoid, and intraventricular he- 
morrhage. 

Epidural hematoma (EDH) and subdural hematoma 
(SDH) are discussed in Table 3. Typical examples are il- 
lustrated in Figs. 5 and 6. 

Traumatic Subarachnoid Hemorrhage 

Traumatic traumatic subarachnoid hemorrhage (SAH) is 
common. Several etiologic mechanisms have been pro- 
posed: (1) superficial cerebral contusion with leakage of 
blood into the subarachnoid space; (2) direct injury to 
leptomeningeal vessels; and (3) intraventricular hemor- 
rhage with reflux through the fourth ventricular foramina 
into the subarachnoid space. Traumatic SAH is an ad- 
verse independent prognostic factor in worsening out- 
comes. It appears that death among patients with trau- 
matic SAH is related to the severity of the initial me- 
chanical damage, rather than to the effects of delayed va- 
sospasm and secondary ischemic brain damage. 

Non-contrast CT is the preferred imaging technique 
for detection of acute traumatic SAH (accuracy, 90%- 
95%). Traumatic SAH is most often focal, overlying the 
site of cortical bruising, or subjacent to a subdural 
hematoma. Blood in the interpeduncular fossa is a reli- 
able indicator of SAH. Diffuse spread of SAH through- 
out all the subarachnoid spaces is less common in head 
trauma. SAH is usually best seen on early CT scans and 
resolves over the following days. 




Fig. 5. Acute left epidural hematoma with subfalcial herniation. 
Non-contrast CT scan upon admission. The hematoma is biconvex, 
and is limited anteriorly by the coronal suture and posteriorly by 
the lambdoid suture (does not cross suture lines). The hematoma 
contains inhomogeneous hypodense areas, indicating blood that is 
not yet clotted. The mass effect causes a subfalcial herniation with 
compression of the left lateral ventricle and dilatation of the right 
lateral ventricle 



Table 3. Epidural versus subdural hematoma 



Epidural hematoma (EDH) 


Subdural hematoma (SDH) 


‘Coup’ side 


‘Contre-coup’ side 


Associated with skull fracture in approximately 90% of cases 


No consistent relationship with skull fractures 


Does not cross suture lines 


Does cross suture lines 


Not limited by falx or tentorium (may extend from supra- to 
infratentorial compartments or across midline) 


Limited by falx and tentorium (confined to supra- or infratentorial 
compartment, does not cross midline) 


Origin: 

• Arterial (majority, due to tearing of one or more branches 
of the meningeal arteries, most commonly the middle 
meningeal artery), 

• Venous (minority, due to laceration of a dural venous sinus, 
e.g. along the sphenoparietal sinus) 


Origin: 

• Venous, due to laceration of superficial bridging cortical veins 


Medical emergency 


May be chronic 


Magnitude of the mass effect caused by EDH is directly 
related to the size of the extracerebral collection 


Magnitude of the mass effect caused by SDH is more often 
associated with underlying parenchymal injury 


CT is preferred imaging technique because: 

• Rapid accessibility 

• Shows both the hemorrhage and the skull fracture 


MRI is preferred imaging technique because: 

• MRI is more sensitive than CT, especially in the detection 
of so-called isodense SDHs which may be difficult to see on CT 


MRI can be useful for: 

• Detection of parenchymal repercussions (edema, mass effect, 
herniations) 


• Multiplanar imaging capability 

• Better definition of multicompartmental nature of SDH 



66 



P.M. Parizel, C.D. Phillips 




Fig. 6a, b. Subacute subdural hematoma in a 7 5 -year-old man. a 
Sagittal SE T1 -weighted image, b Axial TSE T2-weighted image. The 
MR images show the classic appearance of a crescent-shaped left sub- 
dural hematoma. There are multiple internal septations, representing 
strands of fibrovascular granulation tissue, derived from the inner 
(meningeal) layer of the dura. The hematoma extends over the surface 
of the left cerebral hemisphere from the frontal to the occipital region. 
The blood is hyperintense on the T1 -weighted and T2-weighted im- 
ages, indicating the presence of extracellular methemoglobin 



MRI is less useful for the detection of acute traumatic 
SAH. The higher oxygen tension (PO 2 ) in the subarach- 
noid space slows the transformation of oxyhemoglobin 
(Hb 02 ) to paramagnetic breakdown products such as de- 



oxyhemoglobin (Hb) and methemoglobin (HbOH). 
Recent evidence suggests that FLAIR sequences are 
more useful than SE or turbo spin echo (TSE) sequences 
in the detection of SAH. Nevertheless, in most centers, 
CT remains the method of choice for the detection of 
SAH in the acute phase. 

Intraventricular Hemorrhage 

Traumatic intraventricular hemorrhage (IVH) can occur 
as a result of tearing of subependymal veins that line the 
ventricular cavities. Most commonly affected are the 
subependymal veins on the ventral surface of the corpus 
callosum and along the fornix and septum pellucidum. 
Rupture of an intracerebral hemorrhage into the adjacent 
ventricle can also cause IVH. The single cell layer, which 
forms the ependymal lining of the ventricles, does not 
constitute a significant barrier to the extension of an in- 
traparenchymal bleed. Finally, IVH can be found due to 
reflux of SAH through the fourth ventricular foramina of 
Luschka and Magendie. 

In trauma patients, one should look for a horizontal- 
ly sedimented blood-CSF level, which is typically ob- 
served in the occipital horns. Even a small amount of 
IVH is well seen on CT. When the intraventricular 
thrombus matures, clot retraction occurs and a hyper- 
dense intraventricular blood clot is observed adjacent to 
the intraventricular CSF. Signal intensities of IVH on 
MRI vary and depend on its age, presence or absence of 
clotting, and whether or not erythrocyte lysis has oc- 
curred. 



Intra-axial Lesions 

Post-traumatic Cerebral Edema 

Post-traumatic cerebral edema with intracranial hyperten- 
sion is a life-threatening secondary traumatic brain le- 
sion. It starts immediately after injury, but massive ede- 
ma usually takes 24-48 hours to develop. It can be asso- 
ciated with intra-axial or extra-axial lesions. Unilateral 
swelling of a cerebral hemisphere is most often sec- 
ondary to an ipsilateral SDH or EDH. 

Cerebral edema leads to compression of intracranial 
blood vessels, thereby causing underperfusion and is- 
chemia of the edematous region or hemispheres. If the in- 
tracranial pressure is not relieved, the brain will gradual- 
ly herniate through the tentorial incisure and the foramen 
magnum (Table 2). This results in compression of the 
brain stem with depression of breathing and cardiac func- 
tion, and eventually leads to death. Cerebral edema is 
more common in children than in adults; in children, 
brain swelling may be the only identifiable feature of 
head injury. 

CT is more sensitive than MRI for the detection of 
hyperacute cerebral edema. Early imaging findings in 
diffuse cerebral edema include: decreased cerebral at- 





Neuroradiological Diagnosis of Craniocerebral and Spinal Trauma: Current Concepts 



67 



tenuation values; diminished gray-white matter differ- 
entiation; increased density of the falx and tentorium 
(due to vascular stasis, associated SDH, SAH, or both); 
downward bowing of the tentorial leaflets, due to 
supratentorial mass effect; effacement of the cortical 
sulci of the cerebral surface; and obliteration of the 
subarachnoid cisterns near the skull base, particularly 
the suprasellar, quadrigeminal plate and ambient cis- 
terns. The cerebellum may appear relatively hyper- 
dense: this is called “white cerebellum” sign. Since the 
majority of relevant CT changes develop within 48 
hours after injury, pathological categorization based on 
an early, control CT scan is useful for prognostic pur- 
poses. 

Edema associated with intracerebral hemorrhagic con- 
tusions often increases dramatically during the days fol- 
lowing the acute event. Therefore, it is not unusual for the 
initial CT scan to show no or only limited edema, and for 
the follow-up examination to reveal massive perilesional 
edema and associated mass effect. 

Cerebral Contusion and Hematoma 

The term cerebral contusion is used to indicate (punc- 
tate) hemorrhages within the brain parenchyma. 
Contusions are often multiple and located near the sur- 
face of the brain; associated SAH is a common finding. 
Traumatic cerebral contusions are most often encoun- 
tered supratentorially. They are caused when the brain 
hits irregularities of the inner skull table or dural folds 
(falx, tentorium). Sites of predilection include anterior 
and inferior frontal lobes, anterior and inferior temporal 
lobes, and gyri around the sylvian fissure. Contusions 
are much less frequent in the cerebellar hemispheres, 
which are protected by the smooth inner surface of the 
thick occipital bone. 

The term cerebral hematoma refers to a well-circum- 
scribed parenchymal hemorrhage. Cerebral hematomas 
tend to be found in the deeper parts of the brain. Delayed 
development of a post-traumatic intracerebral hemor- 
rhage is not imcommon, and should be suspected when 
the patient’s neurologic condition worsens. As the 
hematoma matures, and clot retraction occurs, it be- 
comes surrounded by a hypodense rim of edema; a he- 
morrhagic sedimentation level may develop. Cerebral 
hematomas can spontaneously decompress into the ven- 
tricles, thereby causing IVH. In trauma patients, a deep 
hematoma may be found along with one or more corti- 
cal contusions. 

In acceleration and deceleration brain injuries, intra- 
parenchymal bleeding sites can be categorized as “coup” 
or “contre-coup” injury. Coup injury occurs at the site of 
primary impact, which is identified by the associated 
scalp injuries or skull fractures. Epidural hematoma, 
contusion or laceration of the brain surface often occurs 
at the site of a fracture, especially if it is depressed. 
Contre-coup injury arises on the opposite side. 
Hemorrhagic cerebral contusions are more common at 



the contre-coup side, though both coup and contre-coup 
injuries can be hemorrhagic. 

A severe impact on the stationary head (e.g. a blow 
with a blunt object) results in skull fractures, but gener- 
ally does not cause contre-coup contusions. This is be- 
cause in these cases, the head does not accelerate or de- 
celerate, and there is no brain lag. This knowledge is use- 
ful in distinguishing head injuries due to falls from those 
due to blows. 

On CT images, acute intraparenchymal hemorrhagic 
contusions are recognized as patchy, ill-defined frontal 
or temporal low density lesions, often containing small, 
hyperdense, punctate foci of petechial hemorrhage. 
Lesions may not be seen on an initial CT scan and fol- 
low-up scans are indispensable when the patient’s clin- 
ical condition deteriorates. Over the next few days, as 
clot retraction occurs, the hemorrhagic area becomes 
surrounded by a rim of edematous brain. After surgical 
decompression of an EDH or SDH, hemorrhagic con- 
tusions may become more apparent. Over time, CT 
density values decrease as thrombolysis progresses; 
this may cause the affected area to become almost iso- 
dense with the surrounding normal brain tissue. The 
perilesional edema diminishes. A resolving hematoma 
may enhance in a ring-like pattern after intravenous 
contrast medium administration. In this stage of evolu- 
tion, differentiation from an infarct or tumor may be 
extremely difficult. 

On MRI, the appearance of intraparenchymal hemor- 
rhage is extremely complex. Imaging findings are deter- 
mined by many parameters, such as: age, location and 
size of the hematoma; pulse sequence; magnetic field 
strength; presence or absence of continued bleeding; lo- 
cal tissue pH; oxygen tension (PO 2 ). The MRI appearance 
of intracerebral hemorrhage follows the evolution as de- 
scribed in Table 4. 

Diffuse Axonal Injury (Shearing Injury of the White 
Matter) 

Even with closed head injury, the brain can suffer severe 
damage from shearing injuries caused by acceleration, 
deceleration or rotational forces. The lesions are deter- 
mined by the magnitude of rotational acceleration and the 
difference in density and rigidity between two adjacent 
tissues, especially gray and white matter. Clinically, dif- 
fuse axonal injury (DAI) is characterized in the acute 
phase by impairment or complete loss of consciousness 
from the moment of impact. A typical example is the “up- 
percut” in boxing, which induces a sudden linear and ro- 
tational acceleration of the skull, causing a sudden loss of 
consciousness. Less severe hemispheric DAI can cause 
loss of telencephalic functions: decreased attention span, 
memory loss, concentration difficulties, lower intelli- 
gence quotient (IQ), headaches, seizures, less stress re- 
sistance, behavioral changes. DAI lesions can be found in 
the following sites of predilection (in decreasing order of 
frequency): 




68 



RM. Parizel, C.D. Phillips 



Table 4. Sequential signal intensity changes of intracranial hemorrhage on MRI (1.5 T) 



Intracranial hemorrhage 





Hyperacute 


Acute 


Early subacute 


Late subacute 


Chronic 


What happens 


Blood leaves the 
vascular system 
(extravasation) 


Deoxygenation 
with formation 
of DeoxyHb 


Clot retraction 
and DeoxyHb is 
oxidized to MetHb 


Cell lysis 

(membrane 

disruption) 


Macrophages digest 
the clot 


Time frame 


< 12 hours 


Hours to days 
(weeks in center 
of hematoma) 


A few days 


From 4-7 days 
to 1 month 


Weeks to years 


Red blood cells 


Intact 


Intact, but hypoxic 


Still intact, 
severely hypoxic 


Lysis (solution 
of lysed cells) 


Gone; 

encephalomalacia 
with proteinaceous 
fluid 


State of Hb 


Intracelluar 
OxyHb (Hb02) 


Intracellular 
DeoxyHb (Hb) 


Intracellular MetHb 
(HbOH) (first at 
periphery of clot) 


Extracellular MetHb 
(HbOH) 


Hemosiderin 
(insoluble) and 
ferritin (water soluble) 


Oxidation state 


Ferrous (Fe^^) 
No unpaired e- 


Ferrous (Fe^^) 
4 unpaired e- 


Ferric (Fe^+) 
5 unpaired e- 


Ferric (Fe^^) 
5 unpaired e- 


Ferric (Fe^+) 
2000x5 unpaired e- 


Magnetic 

properties 


Diamagnetic (x<0) 


Paramagnetic (x>0) 


Paramagnetic (x>0) 


Paramagnetic (X>0) 


Superparamagnetic 

(FeOOH) 


SI on T1 -weighted 


images 


~ or 4 


- or i 

No PEDD interaction 


TT 

PEDD interaction 


TT 

PEDD interaction 


~ or 4 

No PEDD interaction 


SI on T2-weighted 
images 


T (high water 
content) 


4.T2PRE 

(susceptibility effect) 


U T2 PRE 
(susceptibility effect) 


TT No T2 PRE 


TT T2 PRE 
(susceptibility effect) 



Hb, hemoglobin; e-, electrons; FeOOH, ferric oxyhydroxide; SI, signal intensity; PEDD, proton-electron dipole-dipole interaction; PRE, 
proton relaxation enhancement 

~ same; T increased, i decreased SI relative to normal gray matter 



1. The hemispheric gray-white matter junction is the 
most common location for DAI, because the peripher- 
al location increases the vulnerability to trauma and 
because of the abrupt change in tissue density between 
the gray and white matter. The frontal and parietal 
lobes are most frequently involved. 

2. The corpus callosum (CC) is the second most common 
location for DAI shearing lesions. The splenium is 
more commonly affected because of its closer proxim- 
ity to the falx. 

3. Basal ganglia and internal capsule shearing injuries. 

4. Brain stem and mesencephalon shearing lesions are 
only observed with more severe injuries; they are al- 
ways associated with multiple hemorrhages in the 
deep white matter and the corpus callosum. Most 
commonly involved is the dorsolateral quadrant of 
rostral brain stem adjacent to the superior cerebellar 
peduncle. Differential diagnosis includes: Duret’s 
hemorrhage of the brain stem in transtentorial her- 
niation. 

5. Cerebellar shearing injuries are infrequent. 

The neuroradiological diagnosis of DAI is difficult 

(Fig. 7). In the acute phase, a non-contrast CT scan may 

reveal small, punctate petechial hemorrhages (Fig. 7a), 



intraventricular blood (shearing of subependymal veins), 
and perimesencephalic subarachnoid hemorrhage. 
However, CT underestimates DAI lesions, because non- 
hemorrhagic lesions are difficult to identify. Therefore, 
when a patient’s neurologic or psychiatric status is worse 
than predicted from the CT findings, MRI must be per- 
formed. MRI is far more sensitive for detecting DAI le- 
sions. FLAIR sequences are useful for the detection of 
non-hemorrhagic lesions and areas of gliosis (Fig. 7b). 
Gradient echo sequences are used to detect the suscepti- 
bility effects of hemosiderin (Fig. 7d). 

Recent evidence suggests that DAI lesions can be hy- 
perintense on diffusion-weighted images, indicating re- 
stricted diffusion (Fig. 7e, f). Traumatic lesions can be 
classified into three categories depending on their signal 
characteristics on diffusion-weighted imaging (DWI) and 
apparent diffusion coefficient (ADC) maps: type 7, DWI- 
and ADC-hyperintense most likely representing lesions 
with vasogenic edema; type 2, DWI-hyperintense, ADC- 
hypointense indicating C3dotoxic edema; type 5, central 
hemorrhagic lesion surrounded by an area of increased 
diffusion. It remains to be determined if this information 
is clinically useful in predicting final outcome and patient 
prognosis. 





Fig. 7a-f. Diffuse axonal injuries in a 14-year-old boy 4 days after a motor vehicle accident, a Axial non-contrast CT scan, b Axial tur- 
bo FLAIR image, c Axial TSE T2-weighted image, d Axial spoiled gradient echo FLASH T2*-weighted image (TE=25 ms), e Axial dif- 
fusion-weighted trace image (b=1000). f Axial apparent diffusion coefficient map. The non-contrast CT scan shows several punctate pe- 
techial hemorrhages at the gray-white matter junction of the frontal lobes. On the turbo FLAIR and T2-weighted images, the lesions are 
hyperintense. On the gradient echo T2*-weighted image, multiple hypointense hemosiderin deposits are seen at the gray- white matter junc- 
tion and in the corpus callosum. The appearance, multiplicity and topographical distribution are typical of hemorrhagic shearing injuries. 
On the diffusion-weighted scan, the lesions are hyperintense, and on the apparent diffusion coefficient map, the lesions are hypointense, 
indicating restricted diffusion, consistent with type 2 lesions 



Ischemia and Infarction 

Post-traumatic ischemia and infarction are common com- 
plications in patients with craniocerebral trauma. The 
causes of post-traumatic ischemia and infarction are: 

- Vasospasm secondary to: 

• Subarachnoid hemorrhage 

• Direct vessel injury (laceration) 

- Extrinsic compression of a blood vessel by: 

• Cerebral herniation (Table 2) 

• Extra-axial mass (e.g. EDH, SDH) 

- Hypoxia and anoxia 

- Thrombosis and distal embolization secondary to: 



• Vascular dissection 

• Fat embolization due to long bone fracture 

Post-traumatic Sequelae 

If trauma to the brain has been focal (e.g. cerebral contu- 
sions and hematomas), localized encephalomalacia (in- 
traparenchymal tissue loss) may result. Areas of en- 
cephalomalacia are often surrounded by a rim of gliosis 
(Fig. 8). Findings on CT scans include one or more lu- 
cent areas of tissue loss; focal dilatation of the ventricle 
nearest to the traumatic lesion is common. On MRI, en- 









70 



RM. Parizel, C.D. Phillips 




Fig. 8a, b. Post-traumatic encephalomalacia and gliosis. Coronal 
turbo FLAIR images through the frontal (a) and temporal (b) lobes. 
MRI performed 4 years after severe head injury. There are areas of 
post-traumatic tissue loss in the basal part of the frontal lobes bi- 
laterally, and in the lateral portion of the right temporal lobe. The 
areas of tissue loss are surrounded by gliosis, which is hyperintense 
on the FLAIR images. In addition, there are old diffuse axonal in- 
juries, seen as gliotic foci at the gray-white matter interface, e.g. in 
the upper part of the left frontal lobe 



cephalomalacia and gliosis are of high signal intensity on 
T2-weighted images, and are often indistinguishable. 
FLAIR sequences are most helpful to differentiate tissue 
loss from gliosis. Moreover, a gradient echo sequence is 
of value to detect hemosiderin deposition. 

More diffuse trauma can result in generalized atrophy 
of one or both hemispheres, with enlargement of sulci 



and ventricles. Post-traumatic atrophy is observed as dif- 
fuse, non-focal enlargement of the intracranial CSF 
spaces. Diffuse ventricular enlargement can be due to 
communicating hydrocephalus (e.g. decreased CSF ab- 
sorption due to adhesions in the subarachnoid space after 
SAH or meningitis). Focal ventricular enlargement is 
most often secondary to central tissue loss (“ex vacuo”). 

Vascular Injuries 

Traumatic carotid artery-cavernous sinus fistula (CCF) 
is caused by a wall defect in the cavernous portion of the 
internal carotid artery (ICA), thus allowing a direct com- 
munication with the adjacent cavernous sinus. The in- 
creased arterial inflow into the cavernous sinus leads to 
dilatation of the superior ophthalmic vein, the facial 
veins, and the internal jugular vein. Clinical findings in- 
clude pulsating exophthalmos, chemosis, conjunctival 
edema, restricted ocular mobility, and persistent bruit. 
The most common CT and MRI findings are widening of 
the affected cavernous sinus (convex lateral margin), and 
dilatation of the superior ophthalmic vein. MR angiogra- 
phy can be used to demonstrate the venous widening. 

Post-traumatic aneurysms are infrequent complica- 
tions of head trauma. The most common locations in- 
clude the cervical, petrous, and cavernous ICA. The dis- 
tal anterior and middle cerebral arteries are less com- 
monly affected. Basal skull fractures, penetrating in- 
juries, or shearing stress (e.g. against a dural margin) are 
the primary causes of post-traumatic cerebral aneurysms. 

Traumatic vascular dissections are caused by the de- 
velopment of a hematoma within the intima; this results 
in splitting of the vessel wall and causes a false lumen 
within the media. Vascular dissection may lead to lumi- 
nal occlusion or distal embolization. Dissections most 
commonly occur in the internal carotid (60%) or verte- 
bral (20%) arteries; involvement of internal carotid and 
vertebral arteries is seen in up to 10% of cases. Traumatic 
dissection can be caused by blunt or, less frequently, pen- 
etrating trauma to the neck. In cases of “spontaneous” 
dissection, there is often a non-recalled or trivial trauma 
in the history, and if not, a primary arterial disease should 
be considered. The neuroradiological diagnosis can be es- 
tablished by different techniques: 

- Catheter angiography shows a “flame-like” or “radish 
tail-like” tapering of the vessel lumen; 

- Duplex Doppler ultrasound is being increasingly used 
for the diagnosis of intimal dissections; 

- Spiral CT of the neck with surface rendering and max- 
imum intensity projection (MIP) reconstructions can 
be used as an alternative to catheter angiography; 

- MRI should include an axial T1 -weighted sequence 
through the upper neck and skull. These images must 
be carefully studied to detect a crescentic area of high 
signal intensity, which represents the subintimal 
hematoma in the wall of the internal carotid artery. 
Findings can be confirmed by MR angiography. 





Neuroradiological Diagnosis of Craniocerebral and Spinal Trauma: Current Concepts 



71 



CSF Leaks and Pneumocephalus 

A post-traumatic CSF leak occurs as the combined result 
of a dural tear and a bone fracture. It can be the result of 
penetrating trauma (bullet wounds, stabbing) or blunt trau- 
ma (with skull base fractures). CSF leakage into the 
paranasal sinuses or nasal cavity is associated with frac- 
tures of the anterior cranial fossa: ethmoid, posterior wall 
of frontal sinus, planum sphenoidale or cribrifrom plate. 
CSF leakage into the middle ear is associated with frac- 
tures of the floor of the middle cranial fossa extending in- 
to the tegmen tympani. Otorrhea only occurs if the tym- 
panic membrane is perforated or ruptured. If the tympanic 
membrane is intact, the CSF drains via the eustachian tube 
into the rhinopharynx, and rhinorrhea occurs. High-reso- 
lution CT images of the skull base and petrous bones with 
thin sections and bone algorithm images are useful for pre- 
cise loealization of the fractures. The presence of intracra- 
nial air bubbles (pneumocephalus) is an ominous finding. 

Infections 

In non-penetrating head trauma, meningitis can occur as 
the result of an open calvarial fracture, a skull base frac- 
ture, or a post-operative craniotomy defect. Meningitis 
may progress to cerebritis and brain abscess. If the abseess 
ruptures into the ventrieular system, ventriculitis will de- 
velop. Ventriculitis and meningitis are frequently followed 
by obstructive hydrocephalus. In penetrating head trauma, 
infection is caused by debris (e.g. scalp, hair, foreign ma- 
terial) which is carried into the brain by a projeetile. 

Diabetes Insipidus 

Pituitary dysfunction, especially diabetes insipidus, can 
occur as a result of trauma. Transient diabetes insipidus 
usually develops within the first week after trauma and is 
probably due to a contusion of the neurohypophysis. 
Permanent diabetes insipidus indicates structural damage 
to the pituitary gland, the pituitary stalk or the neurose- 
cretory nuclei of the hypothalamus. One should look for 
fractures involving the floor of the sella, hemorrhage 
within the neurohypophysis, transection or laceration of 
the pituitary stalk, petechial hemorrhages in the hypothal- 
amus and elevated intracranial pressure. Delayed onset di- 
abetes insipidus arises months after trauma and should 
suggest the possibility of optochiasmatic arachnoiditis. 

CT should be used to exclude hemorrhages in the 
suprasellar region or skull base fractures extending into 
the sellar floor. MRI shows absence of the normal hyper- 
intense signal in the posterior pituitary lobe. 

Leptomeningeal Cysts 

Leptomeningeal cysts are rare complications of pediatric 
skull fractures. Herniation of the leptomeninges through 



the skull fracture and associated dural tear prevent normal 
healing of the fracture margins. The systolie-diastolie pul- 
sation of the brain and CSF produces fracture diastasis. 
The result is a calvarial defect, which usually becomes 
visible 3-5 months after injury. Leptomeningeal eysts are 
also known as “growing fractures”, because of their ten- 
dency to increase in size over time. On plain X-ray films, 
a skull defect with indistinct, scalloped margins is seen. 
On CT, a CSF density cyst adjacent to or in the skull is 
observed. The cyst is caused by subarachnoid fluid being 
trapped in the herniated tissue, probably secondary to 
arachnoidal adhesions. On MRI, the cyst is isointense 
with CSF and communieates with the subarachnoid space. 
Frequently, there is an underlying area of encephalomala- 
eia, due to compression of the cerebral cortex by the cyst. 

Spinal Injury 

Spinal trauma is a potentially devastating form of trauma, 
which may be accompanied by significant neurologic in- 
jiuy, including paraplegia, quadriplegia, or death. Patients 
who present with complete spinal cord injuries, without dis- 
cemable motor or sensory preservation on neurologic ex- 
amination, have a diminishing hope for a positive outcome. 
On the other hand, patients who present with an incomplete 
injury may regain a large amount of useful function, or be 
spared the progression to complete injiuy with rapid diag- 
nosis and treatment of fracture fragments, hematomas, or 
other lesions that compress the spinal cord. The role of the 
radiologist in this setting is clear: depict the spinal axis 
rapidly and accurately, and guide potential surgical decom- 
pression. Both CT and MRI have important roles to play. 

The spine segment in which CT has played a eritical 
role in the rapid assessment of the traumatized patient is 
the cervical spine. The difficulty in “clearing” the cervical 
spine in trauma patients is well known to most radiologists. 
Despite swimmers views, repeated attempts at open-mouth 
odontoid views, and other permutations of imaging, it is 
often difficult to depict the entirety of the cervical spine to 
a satisfactory extent, allowing the radiologist to exclude 
fractures which may prove significant. There was early 
adoption of the teclmique of thin-section CT with refor- 
mation into the sagittal or coronal plane to evaluate the 
spine, and the early literature was favorable. The wide- 
spread availability of first helieal CT, and subsequently 
multidetector CT refined the technique, and allowed the 
rapid acquisition of data sets which provided confidence in 
diagnosis and increased utilization. It is the policy of many 
major trauma centers in this era to solely evaluate the cer- 
vical spine in the case of major trauma with an MDCT 
study (Fig. 9). We have utilized this technique in the set- 
ting of major trauma for several years now, without a sig- 
nificant misdiagnosis. The only limitation of this technique 
is the inability to provide screening for ligamentous injury. 
CT provides overall superior depiction of the bony anato- 
my of the spinal canal in the trauma patient. It also can de- 
pict significant soft tissue abnormalities, such as traumat- 




72 



P.M. Parizel, C.D. Phillips 



Fig. 9. Multidetector 
CT of the cervical 
spine (sagittal refor- 
matted image) in a 
patient with a C7 
fracture, not seen on 
plain radiographs. 
The height of the 
vertebral body is de- 
creased, the posterior 
wall is displaced 
backwards, with nar- 
rowing of the anteri- 
or-posterior diameter 
of the spinal canal. It 
is now the policy of 
many major trauma 
centers to evaluate 
the cervical spine in 
the case of major 
trauma with a multi- 
detector CT study 



ic disk herniations, significant epidural hemorrhage, and 
other injuries. It is clear that MRI is superior in this regard, 
but the review of spine CT in a trauma patient should in- 
clude careful review of the soft tissue windows. 

CT of the thoracic and lumbar spine is commonly per- 
formed to evaluate suspicious levels on plain film studies, 
or to evaluate the patient with a known level of injury. 
There is little literature on the utilization of CT to the ex- 
clusion of plain film studies in these areas, however, as 
has been the case in the cervical spine. We are often asked 
to reformat data sets on multitrauma patients who have 
undergone chest, abdomen and pelvic CT studies to eval- 
uate the spine. The images that are obtained by reformat- 
ting this data are often adequate to exclude significant 
vertebral body fractures. As with the cervical spine, re- 
formatted sagittal and coronal images are also helpful to 
demonstrate abnormalities in alignment, and to clarify the 
nature of fractures that are seen on the axial images. 

MRI has also gained in importance with its increased 
availability for the emergency room physician. It is appar- 
ent that the depiction of the spinal cord is of primary im- 
portance, and with the adoption of MRI, the utility of 
myelography and post-myelography CT has diminished to 
the point of vanishing (in the absence of contraindications 
to MRI). MRI is capable of depicting the vertebra and sup- 
porting structures, intervetebral disks, the spinal cord and 
nerve roots, trauma-associated injuries such as hemorrhage 
(Fig. 10), traumatic disk herniations, and primary cord in- 
jury such as hematomas, edema, and even cord transection. 
Any patient with presumed spinal cord injury should un- 
dergo emergent MRI study. MRI is superior at depicting 
the previously mentioned lesions and guides surgical man- 
agement in these patients. Careful clinical examination 
with a determined level of injury is an excellent means of 




Fig. 10a, b. Extension-distraction fracure at C5-C6 level with 
epidural hematoma. The patient is a 54-year-old man, injured in a 
motor vehicle accident, with rapidly progressive neurologic deficit. 
MRI was performed on a 0.2 tesla open system, a Sagittal Tl- 
weighted image, b Sagittal T2-weighted image. The anterior col- 
umn of the spine is disrupted and the C5 and C6 vertebral bodies 
are distracted. Extension-distraction injury occurs when hyperex- 
tension forces are applied to the spine. This injury is unstable. An 
epidural hematoma is located in the anterior epidural space, dis- 
placing and compressing the spinal cord 



directing the level to be studied. Many trauma protocols 
may also mandate evaluation of the other spinal segments 
to exclude additional injury which may be masked by a 
higher level spinal cord injury. The sensitivity of MRI for 
not only the soft tissue injuries associated with trauma is 
well known, but MRI may also demonstrate changes with- 
in the bone marrow of traumatized vertebrae which are in- 
apparent on plain film studies, such as bone contusions. 
MRI is also sensitive and specific for ligamentous injury 
in the trauma setting. We have used MRI to provide a “lig- 
ament screen” exam for major trauma patients for several 
years now, with consistent results. The typical exam proto- 
col for this purpose includes sagittal T1 -weighted, sagittal 
gradient recalled T2*-weighted, and sagittal short inver- 
sion-time inversion recovery (STIR) images, as well as ax- 
ial images. Edema in the interspinous or supraspinous lig- 
aments is particularly conspicuous on STIR images. Some 
observers may prefer fat-suppressed T2-weighted images, 
which provide similar conspicuity of the changes of liga- 
mentous injury. Typical fast spin echo T2-weighted images 
are not adequate for the purpose of ligament evaluation, as 
the high signal of fat in the posterior paraspinous region 
obscures the edema. 



Suggested Reading 

Gean AD (1994) Imaging of head trauma. Raven, New York 
Gentry LR (2002) Head trauma. In: Atlas SW (ed) Magnetic reso- 
nance imaging of the brain and spine, 3rd edn. Lippincott- 
Raven, Philadelphia New York, pp 1059-1098 (Chapter 20) 






IDKD 2004 



Nontraumatic Neuroemergencies 

J.R. Hesselinki, S. Atlas^ 

^ Neuroradiology Section, UCSD Medical Center, San Diego, CA, USA 
^ Department of Radiology, Stanford University Medical Center, Stanford, CA, USA 



Introduction 

Several clinical presentations require emergent neu- 
roimaging to determine the cause of the neurological 
deficit and to institute appropriate therapy. Time is 
critical because neurons that are lost cannot be re- 
placed. Generally, the clinical symptoms are due to 
ischemia, compression, or destruction of neural ele- 
ments. The two primary imaging modalities for the 
central nervous system (CNS) are computed tomog- 
raphy (CT) and magnetic resonance imaging (MRI). 
CT is fast and can readily visualize fractures, hem- 
orrhage, and foreign bodies. Otherwise, in patients 
who can cooperate for the longer imaging study, 
MRI provides better contrast resolution and has 
higher specificity for most CNS diseases. This paper 
discusses the five major categories of nontraumatic 
neuroemergencies. 

Seizure or Acute Focal Neurological Deficit 

Arterial Thrombosis and Occlusion 

Thrombotic strokes may occur abruptly but the clinical 
picture often shows gradual worsening over the first few 
hours. Primary causes of arterial thrombosis include ath- 
erosclerosis, hypercoagulable states, arteritis, and dis- 
section. Secondary compromise of vascular structures 
can result from traumatic injury, intracranial mass effect, 
neoplastic encasement, meningeal processes, and va- 
sospasm. 

Arterial Embolus 

Embolic strokes characteristically have an abrupt onset. 
After a number of hours, there may be sudden improve- 
ment in symptoms as the embolus lyses and travels more 
distally. The source of the embolus is usually either the 
heart (in patients with atrial fibrillation or previous my- 
ocardial infarction) or ulcerated plaques at the carotid bi- 
furcation in the neck. 



Arterial Dissection 

Relatively minor trauma is sufficient to cause an arterial 
dissection, or the dissection can occur spontaneously. 
Spin echo images, especially T1 -weighted images with 
fat suppression, should also be obtained because they are 
sensitive for detecting intramural hemorrhage. The typi- 
cal appearance of an oval-shaped hyperintense area with 
an eccentrically placed flow void may provide convincing 
evidence for a dissection. Magnetic resonance angiogra- 
phy (MRA) may demonstrate complete occlusion or on- 
ly narrowing of the arterial lumen. MRA is useful for fol- 
lowing a dissection to look for recanalization of a com- 
plete occlusion or resolution of the vascular compromise 
caused by the intramural thrombus [1]. 

Hypotension and Hypoxia 

Hypotension can be cardiac in origin or result from blood 
volume loss or septic shock. Anoxic or hypoxic events are 
usually related to respiratory compromise from severe 
lung disease, perinatal problems, near drowning, high al- 
titude exposure, carbon monoxide inhalation, or CNS- 
mediated effects. 

Venous or Sinus Occlusion 

Thrombosis of the cerebral venous sinuses has multiple 
etiologies, including hypercoagulable states, pregnancy, 
sepsis, dehydration, paranasal sinus infection, and neo- 
plastic invasion. Occlusion of the venous sinuses results 
in cerebral venous engorgement, brain swelling, and in- 
creased intracranial pressure. If the thrombosis extends 
retrogradely and involves the cortical veins, secondary 
cerebral infarction can occur. 

Acute thrombus is hyperdense on CT and may be de- 
tected within one of the major sinuses or cortical veins. 
The other classic sign is the "empty delta" sign due to 
nonfilling of the superior sagittal sinus on a contrast scan. 
Nonetheless, MRI is far superior for diagnosing abnor- 
malities of the cerebral veins and sinuses. Normally, the 
dural sinuses have sufficient flow to exhibit a flow void. 




74 



J.R. Hesselink, S. Atlas 



If that flow void is missing or if the sinuses are hyperin- 
tense, thrombosis should be suspected. One must be care- 
ful to exclude the possibility of any in-flow enhancement 
effect. The diagnosis must be confirmed with gradient 
echo techniques or MRA. Phase-contrast MRA is the pre- 
ferred technique because it is not adversely affected by 
intraluminal clot. 

Associated parenchymal infarcts are found in the areas 
of venous abnormalities, and the infarcts are often hem- 
orrhagic because arterial perfusion to the damaged tissue 
is maintained. In cases of superior sagittal sinus throm- 
bosis, the infarcts are typically bilateral and in a 
parasagittal location. 

Cortical Mass Lesion 

Any lesion that irritates the cortical neurons can be a 
source of seizures. Neoplasms, encephalitis, meningitis, 
abscess, and hemorrhage are the more common causes of 
new-onset seizures. 



Worst Headache of Life 

Subarachnoid Hemorrhage 

The incidence of congenital aneurysms in the general 
population is about l%-2%. Clinically, a ruptured 
aneurysm presents as sudden onset of severe headache. In 
cases of subarachnoid hemorrhage, the most common 
aneurysms (38% of all cases) are posterior-communicat- 
ing, while anterior-communicating anerysms represent 
36% and middle cerebral aneurysms represent 21%. 
These three locations account for 95% of all ruptured 
aneurysms. The basilar artery accounts for only 2.8% and 
posterior fossa aneurysms are even less common. 

The CT scan is important, first of all, to document the 
subarachnoid hemorrhage and to assess the amount of 
blood in the cisterns. Detection of subarachnoid blood is 
dependent on how early the scan is obtained. Data in the 
literature vary from 60% to 90%. If the scan is obtained 
within 4-5 days, the detection rate is high. Second, CT 
helps localize the site of the aneurysm. This can be done 
by the distribution of blood within the cisterns and also 
with dynamic scanning following an intravenous bolus of 
contrast medium. Third, CT is important to evaluate com- 
plicating factors such as cerebral hematoma, ventricular 
rupture, hydrocephalus, cerebral infarction, impending 
uncal herniation and re-bleed. 

Conventional MRI sequences are insensitive for de- 
tecting subarachnoid hemorrhage. Clots within cisterns 
can be detected, but in general, MRI is not the procedure 
of choice in the workup of patients with subarachnoid he- 
morrhage. Due to the flow void phenomenon, aneurysms 
about the circle of Willis can be identified on spin echo 
MR images [2]. With fluid-attenuated inversion recovery 
(FLAIR) sequences, the cerebrospinal fluid (CSF) is 
dark, so that subarachnoid hemorrhage can be seen more 



easily. These sequences may be helpful for detecting sub- 
arachnoid blood in the posterior fossa where CT has dif- 
ficulty [3]. 

Acute Meningitis 

Bacterial meningitis is an infection of the pia and arachnoid 
and adjacent cerebrospinal fluid. The most common organ- 
isms involved are Haemophilus influenzae, Neisseria 
meningitidis (meningococcus) and Streptococcus pneumo- 
niae. Patients present with fever, headache, seizures, al- 
tered consciousness and neck stiffness. The overall mortal- 
ity rate ranges from 5% to 15% for H. influenzae and 
meningococcal meningitis to as high as 30% with strepto- 
coccal meningitis. In addition, persistent neurologic 
deficits are found in 10% of children after H. influenzae 
meningitis and in 30% of patients with streptococcal 
meningitis. 

The ability of nonenhanced MRI to image meningitis 
is extremely limited, and the majority of cases appear 
normal or have mild hydrocephalus. In severe cases, the 
basal cisterns may be completely obliterated, with high 
signal intensity replacing the normal CSF signal on pro- 
ton density images. Intermediate signal intensity may be 
seen in the basal cisterns on T1 -weighted images in these 
cases. Meningeal enhancement often is not present, un- 
less a chronic infection develops [4]. 

Fungal organisms can start as meningitis or cerebral 
abscess, or can invade directly from an extracranial com- 
partment. Coccidioidomycosis is endemic to the Central 
Valley region of California and desert areas of the south- 
western United States. Infection occurs by inhalation of 
dust from soil usually heavily infected with arthrospores. 
Primary coccidioidomycosis, a pulmonary infection, is 
followed by dissemination in only about 0.2% of im- 
munocompetent patients. Central nervous system in- 
volvement most often represents meningitis, but cerebral 
abscess and granuloma formation can also occur [5]. 
Other fungal infections are primarily found in immuno- 
compromised hosts. 

Migraine 

Migraine headaches can be severe and unrelenting. At 
presentation, the severity of the headache may raise the 
clinical question of possible subarachnoid hemorrhage or 
acute meningitis. Patients with known migraine may also 
develop atypical headaches. 

Acute or Increasing Confusion and Obtundation 

Obstructive Hydrocephalus 

Acute obstructive hydrocephalus is caused by compres- 
sion of the ventricular system to the point of obstructing 
the outflow of CSF. The common locations of blockage 




Nontraumatic Neuroemergencies 



75 



are at the foramina of Monro, the cerebral aqueduct, and 
the outlets of the fourth ventricle. Possible causes include 
tumor, abscess, ventriculitis, and hemorrhage. Brain in- 
jury or cerebral infarction with massive vasogenic edema 
can also cause obstructive hydrocephalus. 

Brain Stem or Basal Ganglia Hemorrhage 

Most large deep hemorrhages in the brain are associated 
with hypertension. The criteria for diagnosing hyperten- 
sive hemorrhage include a hypertensive patient, 60 years 
of age or older, and a basal ganglia or thalamic location 
of the hemorrhage. CT or MRI is the procedure of choice 
for evaluating these patients. Arteriography is necessary 
only if one of these criteria is missing. Hypertensive he- 
morrhages are often large and devastating. Since they are 
deep hemorrhages and near ventricular surfaces, ventric- 
ular rupture is common. One-half of hypertensive hem- 
orrhages occur in the putamen, 25% in the thalamus, 10% 
in the pons and brainstem, 10% in the cerebellum, and 
5% in the cerebral hemispheres. 

Brain Herniation 

As with hydrocephalus, any large mass lesion or process 
with prominent vasogenic edema can produce brain her- 
niation. With large frontal or parietal lesions, subfalcine 
herniation is common. Also, any large hemispheric lesion 
can result in medial migration of the temporal lobe and 
subsequent inferior herniation through the tentorial in- 
cisura. Subfalcine herniation can compress the ipsilateral 
anterior cerebral artery, leading to brain infarction, 
whereas temporal lobe herniation commonly compresses 
the contralateral posterior cerebral artery, causing an oc- 
cipital infarct. Diffuse brain swelling or posterior fossa 
masses can result in herniation of the cerebellar tonsils 
and brain stem inferiorly through the foramen magnum. 

Encephalitis 

Encephalitis refers to a diffuse parenchymal inflamma- 
tion of the brain. Acute encephalitis of the non-herpetic 
type presents with signs and symptoms similar to 
meningitis but with the added features of any combina- 
tion of convulsions, delirium, altered consciousness, 
aphasia, hemiparesis, ataxia, ocular palsies and facial 
weakness. The major causative agents are arthropod- 
borne arboviruses (Eastern and Western equine en- 
cephalitis, St. Louis encephalitis, California virus en- 
cephalitis). Eastern equine encephalitis is the most seri- 
ous but fortunately also the least frequent of the ar- 
bovirus infections. The Enteroviruses, such as coxsack- 
ievirus and echoviruses, can produce a meningoen- 
cephalitis, but more benign aseptic meningitis is more 
common with these organisms. MRI reveals hyperinten- 
sity on T2-weighted scans within the cortical areas of 
involvement, associated with subcortical edema and 
mass effect. 



Herpes simplex is the commonest and gravest form of 
acute encephalitis with a 30%-70% fatality rate and an 
equally high morbidity rate. It is almost always caused by 
type 1 virus except in neonates where type 2 predomi- 
nates. Symptoms, including hallucinations, seizures, per- 
sonality changes and aphasia, may reflect the propensity 
to involve the inferomedial frontal and temporal lobes. 
MRI has demonstrated positive findings in viral en- 
cephalitis as soon as 2 days after s 5 miptoms onset, more 
quickly and definitively than CT. Early involvement of 
the limbic system and temporal lobes is characteristic of 
herpes simplex encephalitis. The cortical abnormalities 
are first noted as ill-defined areas of high signal on T2- 
weighted scans, usually beginning unilaterally but pro- 
gressing to become bilateral. Edema, mass effect and gy- 
ral enhancement may also be present. Since MRI is more 
sensitive than CT for detecting these early changes of en- 
cephalitis, we hope that it will improve the prognosis of 
this devastating disease [6]. 

Meningitis 

As described previously, in addition to severe headache, 
patients with acute meningitis commonly present with 
fever, seizures, altered consciousness and neck stiffness. 
Most of these cases are bacterial in origin, but tuberculo- 
sis and fungal infections can also present acutely. 

Metabolic and Toxic Disorders 

Whenever a patient presents to the emergency depart- 
ment, the possibility of ingestion of drugs or other toxic 
substances must be considered. Narcotics and sedatives 
generally produce respiratory depression, which can lead 
to global cerebral hypoxia. Some toxic agents specifical- 
ly target the basal ganglia or the white matter. In diabet- 
ic patients, the possibility of an insulin overdose and hy- 
poglycemia must be considered. 

Acute or Progressive Visual Deficit 

Monocular Deficit 

Monocular visual loss can be caused by anything anterior 
to the optic chiasm that blocks light from the retina or 
compresses the optic nerve. Ocular diseases, such as reti- 
nal detachment and ocular hemorrhage, are generally first 
evaluated by direct visualization with fimdoscopy or by 
ultrasound. A mass compressing the optic nerve or caus- 
ing severe proptosis can cause a visual deficit. Severe 
proptosis and stretching of the optic nerve can compro- 
mise the arterial supply to the nerve. Finally, intrinsic op- 
tic nerve lesions, such as tumors, ischemia and inflamma- 
tion, are other causes of visual loss. Infraorbital diseases 
are evaluated equally well by CT and MRI. For intracra- 
nial disease, MRI is the imaging procedure of choice. 




76 



J.R. Hesselink, S. Atlas 



Bitemporal Hemianopsia 

This visual deficit is caused by chiasmatic compression, 
usually by a mass in the suprasellar cisterns. Differential 
diagnosis includes all tumors and inflammatory condi- 
tions that can occur in the suprasellar region. 

Homonymous Hemianopsia 

The most common cause of homonymous hemianopsia 
is ischemia in the distribution of the posterior cerebral 
artery that supplies the calcarine cortex of the occipital 
lobe. Mass lesions can also compress the geniculate 
ganglion or the optic radiations in the temporo-occipital 
region. 

Acute and Progressive Myelopathies 

Epidural Hemorrhage 

Most epidural hemorrhages are post-traumatic or post- 
operative events. Patients who are receiving anticoagula- 
tants are at increased risk for epidural hemorrhage. The 
introduction or presence of an epidural catheter also in- 
creases the risk of both hemorrhage and infection. 

Epidural Abscess 

Most epidural abscesses are associated with diskitis or 
osteomyelitis, however, isolated infections of the epidur- 
al space can occur. The diagnosis of epidural abscess can 
be a challenge for both the clinician and radiologist. 
Patients may present with back pain or radicular pain. 
Fever and leukocytosis may be mild. Early diagnosis and 
prompt therapy are critical for favorable patient outcome. 

The imaging findings can be quite subtle on plain Tl- 
and T2-weighted images. During the cellulitis stage, the 
first sign of infection is thickening of the epidural tissues, 
which are initially isointense on T1 -weighted images and 
moderately hyperintense on T2-weighted images. When 
liquefaction occurs, the abscess cavity becomes hy- 
pointense and more hyperintense on Tl- and T2-weight- 
ed images, respectively. Detection of the infectious 
process is easier on gadolinium-enhanced scans. The in- 
flamed tissues are vascular and enhance with gadolinium. 
On both T2-weighted images and enhanced Tl -weighted 
images, fat suppression increases the contrast between 
the infectious process and normal tissues. The abscess 
cavity does not enhance, and appears as thin linear region 
of hypointensity surrounded by the enhancing cellulitis 
on sagittal images. The abscess cavity has an oval con- 
figuration on axial images. 



Tumor 

Epidural tumor usually extends from the spine, and the 
vast majority of spine tumors are metastases. The com- 
mon primary tumor sites are lung, breast, and prostate. 
Occasionally, the epidural space may be directly seeded 
by lymphoma or leukemia. Spinal cord tumors and other 
intradural tumors (schwannoma and meningioma) may 
present with progressive myelopathy. 

Inflammatory Diseases 

Several demyelinating diseases are associated with trans- 
verse myelitis and acute myelopathy. In addition to clas- 
sic multiple sclerosis, post-viral syndromes and Guillain- 
Barre syndrome are in the differential diagnosis. In pa- 
tients infected with human immunodeficiency virus 
(HIV), the two primary diseases to consider are epidural 
abscess and cytomegalovirus (CMV) pol 5 Tadiculopathy. 

Ischemia 

Spinal cord ischemia is rare. It is usually associated with 
spinal and paraspinal tumors or surgical procedures on 
the spine and aorta that may compromise the blood sup- 
ply to the cord. 

Cervical or Thoracic Disk Extrusion 

Disk extrusions in the cervical and thoracic spine, if suf- 
ficiently large, can compress the spinal cord and produce 
a myelopathy. Accompanying cord edema can exacerbate 
the problem. Emergent laminectomy and diskectomy may 
be necessary to relieve the cord compression. 

References 

1 . Levy C, Laissy JP, Raveau V et al ( 1 994) Carotid and vertebral 
artery dissections: three-dimensional time-of-flight MR an- 
giography and MR imaging versus conventional angiography. 
Radiology 190:97 

2. Bondi A, Scialfi G, Scotti G (1988) Intracranial aneurysms: 
MR imaging. Neuroradiology 30:214 

3. Noguchi K, Ogawa T, Inugami A, Totoshima H et al (1995) 
Acute subarachnoid hemorrhage: MR imaging with fluid-at- 
tenuated inversion recovery pulse sequences. Radiology 
196:773-777 

4. Chang KH, Han MH, Roh JK et al ( 1 990) Gd-DTPA enhanced 
MR imaging of the brain in patients with meningitis: compar- 
ison with CT. AJNR Am J Neuroradiol 1 1 :69 

5. Wrobel CJ, Meyer S, Johnson RH et al ( 1992) MR findings in 
acute and chronic coccidioidomycosis meningitis. AJNR Am J 
Neuroradiol 13:1241 

6. Tien RD, Felsberg GJ, Osumi AK (1993) Herpesvirus infec- 
tions of the CNS: MR findings. A JR Am J Roentgenol 
161:167 




IDKD 2004 



Imaging the Patient with Seizures 

P. Ruggieri', A. Nusbaum^ 

' Section of MRI, Cleveland Clinic Foundation, Cleveland, OH, USA 
^ Department of Radiology, New York University Medical School, New York, NY, USA 



Introduction 

Seizures occur as a result of excessive, prolonged and 
synchronous electrical discharges of neurons within the 
brain parenchyma that alter neurologic function. Seizures 
may be acute or provoked such as in the case of a patient 
with a recent closed head injury, acute intracranial in- 
flammatory process, or an acute cerebral infarct. The 
term “epilepsy” is applied to chronic, recurrent seizures. 
These seizures may be partial or focal in onset from a cer- 
tain region of the brain such as the parenchyma adjacent 
to a neoplasm. Alternatively, the seizures may be gener- 
alized with simultaneous onset of the abnormal electrical 
activity from both cerebral hemispheres. If the data are 
insufficient to make these distinctions, the seizures are 
listed as unclassified. There is a higher incidence of par- 
tial seizures among all patients with epilepsy, but this 
varies with age. Generalized seizures are more common 
in early childhood while partial seizures increase in inci- 
dence with age such that partial seizures account for 75% 
of seizures in the elderly [1]. 

Imaging studies are requested in patients with seizures 
in order to reveal a causative underlying disease process. 
Identifying an underlying structural lesion (e.g., neo- 
plasm) on imaging studies in patients with intractable 
partial epilepsy dramatically increases the likelihood of a 
seizure-free surgical outcome if the lesion correlates in 
location to the epileptogenic zone suspected on the basis 
of the clinical history, seizure semiology, and electroen- 
cephalographic findings. In patients with generalized 
seizures, imaging may identify developmental abnormal- 
ities, intracranial manifestations of a neurocutaneous syn- 
drome, the sequelae of a remote insult (e.g. closed head 
injury, perinatal hypoxic or ischemic event), or an acute 
process that may ultimately have an impact on overall 
prognosis or may lead to the use of alternative medica- 
tions for seizure control and treatment of the acute incit- 
ing process. 

Neuroimaging of patients with seizures largely relies 
on magnetic resonance imaging (MRI) for routine clini- 
cal studies but may also include computed tomography 
(CT), positron emission tomography (PET), single pho- 



ton emission computed tomography (SPECT), magnetic 
resonance spectroscopy (MRS), and magnetoencephalog- 
raphy (MEG). While noncontrast head CT is frequently 
requested for patients who present to the emergency 
room with new-onset seizures, studies have shown that 
the efficacy is quite limited for both adult and pediatric 
populations in this setting [2, 3]. CT is falsely negative in 
up to 40% of epilepsy patients with seizures and small 
underlying neoplasms or developmental abnormalities 
that account for the seizures [4]. These studies suggest 
that CT should be reserved for patients with new-onset 
seizures who also present with new neurologic deficits, a 
persistent change in neurologic status, fever, known ma- 
lignancies, anticoagulation therapy, recent trauma, persis- 
tent headaches, or a suspicion of acquired immunodefi- 
ciency syndrome. 

As outlined previously, MRI has assumed a dominant 
imaging role in the clinical evaluation of patients with 
partial (focal onset) epilepsy or poorly controlled gener- 
alized epilepsy. Modalities such as PET, SPECT, and 
MRS are largely reserved for problem solving when the 
MRI studies are negative or the clinical and imaging 
findings are somewhat discordant. PET and SPECT have 
recently gained popularity with the new availability of 
PET CT machines. PET is most frequently performed 
with ['*F]2-deoxyglucose (FDG) in epilepsy patients to 
measure cellular glucose metabolism and glucose uptake 
[5]. Studies in epilepsy patients demonstrate regional hy- 
permetabolism during the ictal period (radiopharmaceu- 
tical injected during the seizure or within 2 minutes of the 
end of the seizure) and hypometabolism if the study is 
performed during the interictal period. PET is clearly 
more sensitive for localization when the epileptogenic fo- 
ci are temporal rather than extratemporal in location but, 
in either case, PET demonstrates regional variations in 
cerebral metabolism so the localization of seizure onset 
is generally overestimated by PET. SPECT studies utilize 
Tc99m-hexamethyl amine oxime (Tc^^“-HMPAO) or 
Tc99m-ethyl cysteinate dimer (Tc^^™ ECD) to evaluate the 
relative changes in local blood flow during the ictal and 
interictal periods to localize epileptogenic foci. SPECT 
studies also demonstrate regional variations in seizure pa- 




78 



P. Ruggieri, A. Nusbaum 



tients, are more helpful in temporal lobe epilepsy, and de- 
mand precise data about the timing of the seizure onset 
and the radiopharmaceutical injection for accurate inter- 
pretation. MRS also measures cerebral metabolism but 
can only investigate a specific area of the brain. 
Therefore, a priori knowledge about the location of the 
epileptogenic site is necessary to perform the study. MEG 
is still primarily implemented as a research tool in a few 
larger institutions. 

The strong soft tissue contrast and multiplanar capa- 
bilities of MRI are particularly advantageous for the iden- 
tification and characterization of structural abnormalities 
in patients with epilepsy. Information on the lesion’s sig- 
nal intensity characteristics on Tl- and T2-weighted and 
FLAIR (fluid attenuated inversion recovery) images, pat- 
tern of enhancement with intravenous gadolinium (when 
appropriate) and morphology, together with the age and 
clinical presentation of the patient, may be sufficient for 
clinical management. Not infrequently, the cortical or 
subcortical epileptogenic lesions responsible for the 
seizures are rather subtle or small and are thus difficult 
to characterize with conventional spin echo studies. It has 
therefore become standard practice to incorporate high 
resolution imaging (e.g. MPRAGE, fast or turbo spin 
echo T2) along with the more conventional pulse se- 
quences to enhance the sensitivity of MRI and to permit 
additional image elaboration. 

Adult Epilepsy 

The electroencephalograms of patients with partial 
seizures demonstrate a focal onset of abnormal electrical 
activity, so the primary clinical question is whether there 
is a focal structural abnormality that is inciting the 
seizure activity in the adjacent brain parenchyma. 
Because epilepsy is a chronic process by definition, the 
parenchymal lesions causing the epilepsy are generally 
slowly progressive or static in nature, and supratentorial 
and cortical or subcortical in location. Such lesions in the 
adult population commonly include mesial temporal scle- 
rosis, low-grade neoplasms, vascular malformations, en- 
cephalomalacia related to prior insults (e.g. infarcts) and, 
in young adults, developmental abnormalities. 

Mesial temporal sclerosis, commonly seen in patients 
with temporal lobe epilepsy, consists of neuronal cell loss 
and reactive gliosis in the hippocampal formation, amyg- 
dala, entorhinal cortex, and parahippocampal gyrus. There 
is a strong association with the history of a prolonged 
febrile convulsion during early childhood but it remains 
controversial whether this is a cause or an effect of the 
seizures. The imaging hallmarks (Fig. 1) include asym- 
metric atrophy and loss of the normal internal architecture 
of the head and body of the hippocampal formation and 
prolonged T2-relaxation times in this same distribution 
[6]. There may also be asymmetric volume loss in the ip- 
silateral amygdala, mammillary body, column of the 
fornix and the parahippocampal gyrus, and hypointensity 




Fig. la, b. Mesial temporal sclerosis, a Severe volume loss of the 
body of the right hippocampal formation compared to normal left 
side, b Prolonged T2 relaxation time seen as moderate hyperinten- 
sity in the same distribution on coronal TSE FLAIR 



in the previously mentioned gray matter structures on the 
Tl -weighted gradient echo volume sequence. In view of 
the size of these structures, the abnormal morphology is 
best appreciated on high-resolution, three-dimensional 
(3D) coronal, Tl -weighted gradient echo images perpen- 
dicular to the long axis of the hippocampal formations. 
The T2 findings are best appreciated on coronal FLAIR or 
T2-weighted turbo spin echo images. 

Neoplastic processes are typically low-grade masses 
that are more apt to cause seizures than symptoms relat- 
ed to local mass effect, hydrocephalus, increased in- 





Imaging the Patient with Seizures 



79 



tracranial pressure, or focal neurologic deficits. 
Neoplasms account for seizures in 10%-30% of patients 
with chronic epilepsy [7]. Most commonly, such masses 
include astrocytomas, gangliogliomas, oligoden- 
drogliomas (Fig. 2), and dysembryoplastic neuroepithe- 
lial tumors (DNETs). It may be difficult to distinguish 
between some of these neoplasms on preoperative MRI 
but it is more important to determine that the structural 
lesion is neoplastic and to define the extent of the mass 
and the relationship to eloquent cortex for surgical plan- 




Fig. 2a, b. Oligodendroglioma, a Relatively well defined, irregu- 
lar focus of hyperintensity in the gray and white matter of the tem- 
poral pole on coronal FLAIR, b Mild irregular enhancement pe- 
ripherally with gadolinium administration 



ning purposes. In general, these masses are relatively 
small apd infiltrative, account for only mild localized 
mass effect, have little or more commonly no surround- 
ing vasogenic edema, are variably hyperintense on 
FLAIR and T2-weighted images, and enhance mildly or 
not at all with gadolinium. Notable exceptions to these 
generalizations include pilocytic astrocytomas and pleo- 
morphic xanthoastrocytomas, both of which prominently 
enhance with gadolinium, tend to be better defined, and 
are surrounded by mild edema (Fig. 3). The DNETs are 




Fig. 3a, b. Pilocytic astrocytoma, a Large well-defined right tem- 
poral lobe mass with mild surrounding edema relative to size, b 
Large cystic component with crescentic medial rim of soft tissue 
that enhanced very prominently with gadolinium 





80 



P. Ruggieri, A. Nusbaum 




Fig. 4a, b. Cavernous angioma, a Nodular heterogeneously hyperintense mass in the left superior temporal gyrus without significant mass 
effect, b Peripheral rim of hypointensity more obvious on T2 weighted image related to prior hemorrhage 



also somewhat atypical as they may demonstrate stigma- 
ta of malformations of cortical development (characteris- 
tic ion histological analysis), in addition to the character- 
istics of a primary mass. 

Vascular malformations that cause seizures may be 
true arteriovenous malformations (AVMs) or, more com- 
monly, occult vascular malformations. True AVMs are a 
direct communication between the arterial and venous 
circulations whose nidus is recognized as a cluster of ser- 
piginous flow voids that are commonly supratentorial and 
superficial and may cause localized volume loss in the 
parenchyma due to a steal phenomenon or prior hemor- 
rhage. Preoperatively, these AVMs are classified by the 
size of the nidus, location relative to eloquent cortex, and 
the presence of deep venous drainage [8]. Cavernous an- 
giomas are occult vascular malformations that common- 
ly present with seizures or headaches, are generally iden- 
tified in young adults, and are typically supratentorial and 
subcortical in location. They typically appear as a nodu- 
lar focus of heterogeneous hyperintensity on Tl- and T2- 
weighted images with a peripheral rim of hypointensity 
on the T2-weighted images due to ferritin and hemo- 
siderin deposition from prior repeated parenchymal hem- 
orrhage (Fig. 4). A gradient echo study will make the he- 
morrhagic byproducts more obvious and help to identify 
additional similar foci elsewhere that are easily masked 
on the turbo spin echo images. 

Encephalomalacia is potentially epileptogenic if it is 
supratentorial and cortical or subcortical. Such lesions 
can be recognized by localized or more generalized vol- 
ume loss on a variety of sequences and by the hyperin- 



tense signal on FLAIR and T2-weighted images. The eti- 
ology can be quite variable and may occur as the chron- 
ic sequelae of prior intracranial infections, ischemia, 
trauma or metabolic disorders (Fig. 5). On occasion, the 




Fig. 5. Encephalomalacia from remote HSV infection. Extensive 
volume loss in the right temporal lobe suggestive of prior contu- 
sion but extensive involvement of the mesial temporal structures in 
each temporal lobe, characteristic of herpes simplex virus (HSV) 
infections 





Imaging the Patient with Seizures 



81 



imaging findings can be more specific such as cortical 
volume loss and evidence of old hemorrhage in the sub- 
frontal regions or temporal poles, which implies the 
residua of prior contusions from a closed head injury. 
More commonly, the imaging findings are non-specific 
and it is necessary to rely on the clinical history to define 
the etiology The history and clinical characteristics of the 
epilepsy also provide a sense of the likely extent of in- 
volvement that may not be obvious on imaging and there- 
fore demands closer inspection of the volume acquisition. 
The most important issues are to recognize the lesions as 
encephalomalacia and to define the extent and severity of 
the parenchymal involvement for prognostic and surgical 
planning purposes. The parenchymal damage from in- 
sults such as prior meningitis or closed head injuries may 
be more extensive than would be suggested upon cursory 
review of the spin echo images. If supported by clinical 
parameters, such data frequently indicate that the patient 
is unlikely to be a good surgical candidate. 

Pediatric Epilepsy 

All of the structural lesions discussed previously can cer- 
tainly account for seizures in the pediatric population as 
well. In contrast, the encephalomalacia causing seizures 
in infants and young children may stem from insults dur- 
ing the intrauterine or perinatal period and are frequently 
considerably more extensive than the typical cortical in- 
farct that may cause seizures in the adult population (Fig. 
6). Moreover, insults that occur before the beginning of 
the third trimester will not result in reactive astrocytosis 
that is typical of insults in older children and adults. 
Hence, the hyperintense T2-signal abnormalities cannot 
necessarily serve as imaging cues for encephalomalacia 
in these children. If present, the T2 signal abnormalities 
can be more difficult to recognize in infants due to the re- 
versal of normal contrast in the brain on conventional 
MR pulse sequences in infants with immature myelin. 
The prior insult may also result in a delay in normal 
myelination, further complicating the diagnosis and po- 
tentially causing more diffuse imaging abnormalities. 
Alternatively, the insult to the developing brain may 
cause a malformation of cortical development so there 
may be more than one type of pathology accounting for 
the child’s seizures (dual pathology). 

Malformations of cortical development can be focal, 
lobar, multilobar, hemispheric or more generalized. The 
dysplasia can arise from an insult to the developing brain 
but may be genetically predetermined. A malformation of 
cortical development can arise due to an alteration of the 
normal pattern of programmed cell death, disruption of 
the normal neuronal migration, or defective cortical mat- 
uration or organization [9-12]. If secondary, the ultimate 
type and extent of dysplasia likely depends on the nature 
of the insult during development, the timing of the event 
relative to the normal developmental processes that are 
taking place, and whether there is a local or global effect 



Fig. 6a, b. Peri- 
natal infarct, a 
Full-term infant 
with uncomplicat- 
ed pregnancy and 
caesarian section 
delivery due to po- 
sition of fetus but 
apneic episode 
shortly after deliv- 
ery. Right middle 
cerebral artery 
(MCA) infarct 
compromising 
corpus striatum, 
insular cortex and 
occipital lobe, b 
Small right cere- 
bral hemisphere 
with diffuse subtle 
FLAIR hyperin- 
tensity and hemi- 
spheric hypome- 
tabolism on PET 



on the developing brain. These considerations would nat- 
urally suggest a wide variety of developmental dysplasias 
that may be encountered in children and young adults 
with chronic epilepsy. The various classifications of cor- 
tical malformations will not be discussed in this chapter. 
Instead, this discussion will provide generalizations about 
their imaging characteristics. 

A malformation of cortical development may be sus- 
pected by recognizing a significant variation in the nor- 
mal sulcation pattern in one or multiple regions of the 
brain. This demands not only familiarity with the normal 
surface anatomy of the brain but also with the extent of 
normal variations as many asymmetries likely simply 
represent sulcation “anomalies” rather than “abnormali- 
ties.” This detail is generally only apparent on the thin 
contiguous slices of a high-resolution, gradient echo vol- 
ume acquisition. 

The level of confidence can be improved on imaging 
findings alone if closer inspection of the cortical architec- 
ture demonstrates other asymmetries beyond the sulcation 
pattern. For example, thickened cortex may be apparent on 
the conventional spin echo sequences but correlation with 





82 



R Ruggieri, A. Nusbaum 



the high-resolution 3D acquisition may reveal numerous 
small gyri or broad flat gyri (suggesting polymicrogyria or 
pachygyria) that may not be distinguished on the thicker 
spin echo slices. Even the sagittal T1 -weighted images may 
be especially helpful over the lateral convexities (Fig. 7). 
Alternatively, the cortex may be more subtly dysmorphic, 
such as unusually deep or complex cortical infolding com- 
pared to the corresponding region in the opposite hemi- 
sphere, possibly with localized enlargement of the overlying 
cerebrospinal fluid (CSF) space or the underlying ventricle. 





Fig. 7a, b. Polymicrogyria, a Axial T2-weighted image with asym- 
metric gyri in the right sylvian region with slight loss in gray-white 
distinction, b Parasagittal T1 -weighted image clearly reveals multiple 
small gyri with thickened cortical mantle reflecting polymicrogyria 



When cortical developmental abnormalities are isoin- 
tense to normal tissues, the only visual clue to their pres- 
ence is a morphologic abnormality. In other cases, the mor- 
phologic abnormalities are subtly evident if at all and the 
dysplasia is recognized by slight differences in signal in- 
tensity characteristics in the subcortical white matter with 
or without similar findings in the overlying cortex. 
Importantly, there should be no localized mass effect as this 
might imply neoplasm. The signal abnormalities are gener- 
ally most evident on FLAIR images in mature brains but 
can also be seen on T2-weighted spin echo and gradient 
echo volume studies. The latter two sequences are fre- 
quently more helpful during the first year of life when the 
signal abnormalities may be reversed on these sequences. 
More commonly, the mild hyperintensity in the cortex and 
subcortical white matter on FLAIR or T2-weighted images 
and hypointensity on the gradient echo volume images in 
older patients may cause blurring of the gray-white matter 
junction (Fig. 8). The FLAIR and T2-weighted images may 
also show curvilinear bands of hyperintensity in the region 



Fig. 8a, b. Focal 
malformation of 
cortical develop- 
ment. a Anom- 
alous anterior 
extension of the 
superior aspect 
of the right cen- 
tral sulcus may 
just be normal 
variant, b Further 
axial reconstruc- 
tions of coronal 
volume sequence 
show blurring of 
gray-white junc- 
tion, distinctly 
different from 
adjacent cortex 
and suggesting 
focal dysplasia 







Imaging the Patient with Seizures 



83 



of the subcortical association fibers. When these signal ab- 
normalities extend centrally to the ependymal surface of the 
underlying ventricle in a conical configuration (apex cen- 
trally), the dysplasias are termed transmantle malforma- 
tions of cortical development (Fig. 9). When the malforma- 
tions of cortical development are more extensive such as in 
lesions involving the whole cerebral hemisphere, there may 
be a combination of different imaging findings in the same 
patient in view of the variable underlying histology. 

Another group of extensive parenchymal disorders in 
children with epilepsy includes the various neurocutaneous 
syndromes such as Sturge-Weber syndrome and tuberous 
sclerosis. Sturge-Weber syndrome or encephalotrigeminal 
angiomatosis is thought to arise from the persistence of the 
primordial vasculature present early in the first trimester 
when the ectoderm responsible for the skin of the face and 
the neural tube is contiguous. Sturge-Weber syndrome is 
characterized by a facial port-wine nevus, angioma of the 
choroid, and angioma of the leptomeninges. The MRI find- 
ings are most commonly evident in the parietal occipital 
region of one cerebral hemisphere but can be frontal, holo- 
hemispheric or rarely bilateral and generally correlate with 
the distribution of the port-wine nevus. Leptomeningeal 
enhancement on gadolinium-enhanced T1 -weighted or 
FLAIR images indicates the extent of the pial vascular 
malformation [13, 14]. Generally, there is also evidence of 
less extensive preferential cortical volume loss, hypointen- 
sity in the subcortical white matter on T2-weighted images, 
enlarged medullary veins, absence of the overlying cortical 
veins, thickening of the overlying calvarium, and enlarge- 




Fig. 9. Transmantle malformation of cortical development. FLAIR 
image demonstrates band of hyperintensity radiating from the 
ependymal surface to the cortex and more extensive subcortical hy- 
perintensity along the central sulcus without local mass effect 



ment of the ipsilateral choroid plexus in the atrium of the 
lateral ventricle (Fig. 10). 

Tuberous sclerosis (Boumeville’s disease) is a disorder 
with autosomal dominant transmission characterized by 
mental retardation, epilepsy and adenoma sebaceum, but 
the primary diagnostic criteria include facial angiofibro- 




Fig. 10a, b. Sturge-Weber syndrome, a Asymmetric volume loss 
throughout the right hemisphere with preferential cortical involve- 
ment and hypointensity in the subcortical white matter on T2- 
weighted image, b Diffuse mild leptomeningeal enhancement of 
angioma, asymmetrically large choroid plexus in the atrium, and 
prominent medullary veins 




84 



P. Ruggieri, A. Nusbaum 



mas, ungual fibromas, retinal astrocytomas, cortical tu- 
bers, and subependymal nodules or giant cell astrocy- 
tomas. MRI findings include subependymal hamartomas, 
giant cell tumors, cortical tubers, and radiating white mat- 
ter lesions [15, 16]. Subependymal hamartomas are recog- 
nized as small nodules protruding into the ventricles, most 
commonly along the course of the caudate nucleus. In the 
unmyelinated infant brain, these hamartomas are hyperin- 
tense on T1 -weighted images and hypointense on T2- 
weighted images. In the older child and adult, these nod- 
ules are isointense to white matter on T1 -weighted images, 
iso- or hypointense on T2-weighted images, and demon- 
strate mild if any enhancement with gadolinium. Giant cell 
astrocytomas are similar in appearance but occur in the re- 
gion of the foramina of Monro, enhance prominently with 
gadolinium or iodinated contrast medium, and increase in 
size over time. These masses can rarely degenerate into 
more aggressive neoplasms while the location and propen- 
sity for growth may cause obstructive hydrocephalus. 
Cortical tubers are centered in the subcortical white mat- 
ter; in unmyelinated brain they are hyperintense on Tl- 
weighted images and hypointense on T2-weighted images, 
while in mature brain they are iso- or hypointense on Tl- 
weighted images and hyperintense on T2-weighted images. 
There is generally negligible mass effect and no enhance- 
ment with gadolinium. The white matter lesions are hyper- 
intense on T2-weighted images in mature brain and hyper- 
intense on T1 -weighted images in immature brain; they 
may appear nodular or as radiating bands extending from 
the periventricular region to the overlying cortex (Fig. 11) 




References 

1. So EL (1995) Classifications and epidemiologic considera- 
tions of epileptic seizures and epilepsy. Neuroimaging Clin N 
Am 5(4):5 13-526 

2. Greenberg MK, Barsan WG, Starkman S (1996) Neuroimaging 
in the emergency room patient presenting with seizure. 
Neurology 47:26-32 

3. Maytal J, Krauss JM, Novak G, Nagelberg J, Patel M (2000) 
The role of brain computed tomography in evaluating children 
with new onset of seizures in the emergency department. 
Epilepsia 41(8):950-964 

4. Shields WD (1993) Neuroimaging in the diagnosis and man- 
agement of pediatric epilepsy. In: Dodson WE, Pellock JM 
(eds) Pediatric epilepsy: diagnosis and therapy. Demos, New 
York, pp 99-106 

5. Spencer SS (1994) The relative contributions of MRI, SPECT, 
and PET imaging in epilepsy. Epilepsia 35[Suppl 6]:S72-S89 

6. Jack CR Jr (1993) Epilepsy: surgery and imaging. Radiology 
189:635-646 

7. Britton JW, Cascino GD, Sharbrough FW et al (1994) Low- 
grade glial neoplasms and intractable partial epilepsy: effica- 
cy of surgical treatment. Epilepsia 35:1130-1135 

8. Spetzler RF, Martin DDA (1986) A proposed scheme for grad- 
ing intracranial arteriovenous malformations. J Neurosurg 
65:476-483 

9. Raymond AA, Fish DR, Sisodiya SM et al (1995) Abnormali- 
ties of gyration, heterotopias, tuberous sclerosis, focal cortical 
dysplasia, microdysgenesis, dysembryoplastic neuroepithelial 
tumour and dysgenesis of the archicortex in epilepsy: clinical, 
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118:101-131 

10. Dobyns WB, Truwitt CL (1995) Lissencephaly and other mal- 
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atrics 26:132-147 

11. Barkovich AJ, Kuzniecky RI, Dobyns WB et al (1996) A clas- 
sification scheme for malformations of cortical development. 
Neuropediatrics 27:59-63 

12. Barkovich AJ, Kuzniecky RI, Jackson GD et al (2001) 
Classification system for malformations of cortical develop- 
ment: update 2001. Neurology 57(12): 2168-2178 

13. Benedikt RA, Brown DC, Walker R et al (1993) Sturge-Weber 
syndrome: cranial MR imaging with Gd-DTPA. AJNR Am J 
Neuroradiol 14:409-415 

14. Griffiths PD, Coley SC, Romanaowski CA et al (2003) 
Contrast-enhanced fluid-attenuated inversion recovery imag- 
ing for leptomeningeal disease in children. Am J Neuroradiol 
24:719-723 

15. Braffman BH, Bilaniuk LT, Naidich TP et al (1992) MR imag- 
ing of tuberous sclerosis: pathogenesis of this phakomatosis, 
use of gadopentetate dimeglumine, and literature review. 
Radiology 183:227-238 

16. Baron Y, Barkovich AJ (1999) MR imaging of tuberous scle- 
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20:907-916 



Fig. 11. Tuberous sclerosis. Axial T2-weighted image demonstrates 
small hypointense subependymal nodular hamartomas, hyperin- 
tense subcortical tubers, and hyperintense radiating foci in the in- 
tervening deep white matter throughout both cerebral hemispheres 




IDKD 2004 



Infectious Diseases of the Central Nervous System 

V Dousset 

Neuroradiology Service, CHU Pellegrin, Bordeaux, France 



Introduction 

Infectious diseases affecting humans have greatly de- 
creased in the past decades because of the use of antibi- 
otics and the increased level of hygiene. However, the 
central nervous system (CNS) must be seen has a poten- 
tial target for many organisms that are able to cause se- 
vere diseases with striking symptoms. 

Imaging technology including computed tomography 
(CT) and especially magnetic resonance imaging (MRI) 
have enhanced our ability to characterize infectious 
processes. MRI techniques such as T2-weighted fast 
imaging and fluid-attenuated inversion-recovery 
(FLAIR) make it possible to depict lesions in the brain, 
spinal cord and meninges. More recently, techniques 
such as diffusion-weighted imaging and magnetic reso- 
nance spectroscopy (MRS) have been applied to in- 
flammatory and infectious lesions, bringing new capa- 
bilities for in vivo characterization [1-4]. They have an 
impact on making the diagnosis and understanding the 
disease process. 

The appearance of inflammatory lesions is a reflec- 
tion of multiple factors, including the type of organism, 
mode of spread, host response, and histopathologic 
findings. Infections spread to the CNS by three poten- 
tial ways: 

1 . Hematogenously, either through the choroid plexus or 
through the blood-brain barrier (BBB). It is now the 
most frequent origin of infection in the CNS. 

2. Direct spread from adjacent structures, such as the si- 
nuses, nasopharynx, or mastoid air cells. 

3. Retrograde axoplasmic flow along cranial or peripher- 
al nerves by some viral agents such as herpes. 

The imaging features of CNS infections can be classi- 
fied by the type of organism, location of the lesion, and 
host response. Organisms infecting the CNS include 
viruses, mycotic agents, parasites and bacteria. The le- 
sions may be located in one or several of the following 
sites: cerebrospinal fluid (CSF), meninges, parenchyma, 
arteries, veins and cranial cavities (e.g. sinuses, mastoid). 
It is important in an imaging study to look for several lo- 
cations. 



Finally, the host response depends on the host’s char- 
acteristics: 

{di) Immunocompetent patients (children and adults). 
The response is immunologic and most often symp- 
toms and imaging findings are related to the re- 
sponse rather than to the infectious agent. This 
means that similar imaging features are observed for 
several organisms, making a specific diagnosis 
somewhat difficult. There is now evidence for a 
strong role of the individual’s genetic background in 
the development of an infection in the CNS. Just as 
prions are infectious only in susceptible individuals, 
many organisms are probably infective for some in- 
dividuals and not for others. A transient decrease in 
the level of immunity may also be responsible for 
disease development. 

()o) Immunocompromised patients. This group includes 
patients with particular conditions or pathologies that 
lead to an immunodeficient state; these conditions in- 
clude anticancer chemotherapy, long-term steroid 
therapy, infection with human immunodeficiency 
virus (HIV) and diabetes mellitus. These patients are 
susceptible to infections with opportunistic agents, i.e. 
pathogens that do not cause disease in immunocom- 
petent persons [5]. HIV has infected more than 60 
million people in the world, including 26 million per- 
sons in Africa. In the CNS of HIV positive patients, 
numerous and some very specific agents may devel- 
op: HIV virus. Toxoplasma gondii, JC virus, tuber- 
culosis, cytomegalovirus (CMV), cryptococcus for 
the most frequent. CNS type B lymphoma can also 
develop. In immunocompromised non-HIV patient as 
in HIV patients, agents such as Candida albicans, 
mucormycosis or nocardia may become pathogenic 
for the CNS. 

(c) Newborns. During birth and the first few weeks after- 
wards, newborn infants can be infected by agents pre- 
sent in the mother’s birth channel, for example her- 
pesvirus type 2, Listeria monocytogenes, and urinary 
germs such as E. coli, Proteus and Candida albicans. 

(d) Embryo and fetus. Several infections may develop in 
utero, sometimes leading to death of the embryo or to 




86 



V Dousset 



CNS malformations in the fetus. The most frequent 
agents are Toxoplasma gondii, CMV, rubella virus, 
herpesviruses and HIV [6]. 

(e) Finally, the immune system may be the origin of CNS 
manifestations of systemic infections when the im- 
mune response to the infectious agent cross-reacts 
with constitutive proteins of the CNS. The infectious 
organism is usually absent from the CNS. The most 
sensitive targets are myelin proteins, leading to acute 
disseminated encephalomyelitis (ADEM). ADEM is 
caused by cross-reaction to viruses or bacteria follow- 
ing systemic infection or vaccination. Vasculitis may 
also be of immunologic origin; in this case a response 
to a systemic infection leads to cerebral infarct. Some 
granulomatous diseases (e.g. inflammatory pseudotu- 
mor, sarcoidosis) lead to the abnormal collection of 
normal immune cells in the CNS, mostly in the 
meninges, facial cavities and cavernous sinus. 

I now describe the infections by type of organism af- 
fecting the CNS: viruses, prions, bacteria, parasites, fun- 
gi, granulomatous infections and immunologic diseases. 
The immunologic state of the host and the location of the 
infection are discussed in each section. 



Viral Infections 

The two main types of viral infections of the CNS are 
meningitis and encephalitis. Neurological symptoms de- 
pend on the location of the infection: 

1. Meningitis due to viruses, the most frequent infec- 
tious disease of immunocompetent hosts, has few 
imaging manifestations. Waiting for imaging mani- 
festations may unnecessarily delay the time for lum- 
bar puncture and treatment. Enhancement of 
meninges is rare. 

2. Viral encephalitis is usually associated with seizure, a 
decrease of consciousness or focal symptoms such as 
sensorimotor deficits. Mild mass effect may be seen 
during the acute phase of encephalitis. Enhancement is 
often absent early in the course of acute encephalitis 
unless there is associated meningitis. 

Viruses in Immunocompetent Patients 

Some viruses may affect both immunocompetent and im- 
munocompromised patients, children, adults and neonates. 
These virus belong to the groups of herpesviruses, en- 
teroviruses and arboviruses. 

Herpesviruses are DNA viruses, and many can cause 
CNS infections in humans, including herpes simplex 
viruses 1 and 2, varicella-zoster virus, Epstein-Barr virus, 
and cytomegalovirus [7, 8]. 

- Herpes simplex virus (HSVl) is the most common 
cause of sporadic viral meningo-encephalitis. 
Clinical manifestations include fever, headache, neck 
stiffness, seizures, focal deficits, and depressed men- 



tal state. Because acyclovir therapy is safe, it is rec- 
ommended that the drug be given on the basis of clin- 
ical findings. Encephalitis results from reactivation 
of latent viral infection of the gasserian (fifth cranial 
nerve) ganglion. From here, the infection spreads to 
the parenchyma. The virus has a predilection for the 
medial area of the temporal, frontal and insular lobes. 
On CT, low densities are seen on affected areas. 
There is no enhancement, and only the adjacent 
meninges may show some congestive changes with 
little contrast agent uptake. On MRI, hyperintensities 
are encountered in the temporal, frontal and insular 
areas, and the bilateral nature of the process is fre- 
quently apparent. Initially, the infection may appear 
unilateral on imaging studies, but over time, involve- 
ment of the contralateral temporal and frontal lobes 
becomes apparent. 

- Herpes simplex virus 2 is the most common cause of 
neonatal encephalitis. Infection occurs when the fetus 
passes through the birth canal of a mother with geni- 
tal herpes. Imaging findings reflect rapid brain de- 
struction. In adults, infections with extension to the 
spinal cord have been observed. 

- Varicella-zoster virus produces two distinct clinical 
syndromes, chicken pox and herpes zoster. Diffuse en- 
cephalitis is a rare complication of chicken pox; it is 
more common in adults and is usually mild. Herpes 
zoster may lead to an involvement of peripheral and 
cranial nerves. The affected cranial nerve appears ede- 
matous and swollen, and it will enhance at MRI with 
gadolinium. 

- CMV infection in adults, seen almost exclusively in 
immunocompromised patients, leads to ventriculitis 
and leptomeningitis. Ventriculitis is diagnosed on MRI 
by the presence of enhancement of ventricle surfaces. 
The differential diagnosis is subependymal lymphoma. 
CMV is also the most common cause of congenital en- 
cephalitis. It produces massive brain destruction. 
Infections acquired in the second trimester produce 
cortical dysplasias. 

- Epstein-Barr virus has been linked to diverse entities, 
such as Guillain-Barre syndrome and lymphoma in pa- 
tients with acquired immune deficiency syndrome 
(AIDS). About 5% of the patients with infectious 
mononucleosis develop acute, usually self-limiting en- 
cephalomyelitis. This disorder may be responsible for 
hyperintensities on T2-weighted images of the deep 
supratentorial gray matter and central gray matter of 
the spinal cord. Rapid resolution of the lesions has 
been reported in this disease. 

- Human herpesvirus 6 has been identified as a cause of 
encephalitis and febrile seizure [8]. 

Enterovirus may be responsible for meningitis and 
rarely for encephalitis [1]. In the latter, the spinal cord, 
medulla, pons, mesencephalon, dentate nucleus of the 
cerebellum, and occasionally the thalamus may be affect- 
ed. These structures appear hyperintense on T2-weighted 
images. 




Infectious Diseases of the Central Nervous System 



87 



Location of infection in the rhombencephalon and 
mesencephalon is the predilection of one species of bac- 
teria, Listeria monocytogenes. 

West Nile virus has emerged in the United States as a 
new pathogen causing encephalitis [8]. 

Viruses in Immunocompromised Patients 

The CNS of immunocompromised patients may be in- 
fected by the same viruses affecting immunocompetent 
patients. Additionally, other viruses only develop in im- 
munocompromised patients [5, 9]. The human immunod- 
eficiency virus that causes the depletion in immunity may 
be responsible for encephalitis. Another virus, JC virus, 
can also cause multifocal encephalitis with destruction of 
oligodendrocytes. 

HIV Encephalitis 

HIV-1 is the human RNA retrovirus that causes AIDS. The 
brain is one of the most commonly affected organs. Almost 
all patients have the virus in the CNS, and 10%-15% may 
develop a decrease in mental status or dementia. 

The primary infection with HIV may lead to focal ab- 
normal deep white matter spots recognized as hyperin- 
tensities on T2-weighted images [10]. These nonspecific 
signs should be interpreted cautiously since they are fre- 
quent in many other conditions such as aging, hyperten- 
sion, tabacco use and diabetes. 

The brain parenchyma is one of the sites of residency 
of HIV for several years. During the latency phase, be- 
fore a patient is diagnosed with AIDS, some degree of at- 
rophy may occur. 

When immunodepression is strong, HIV itself causes 
subacute progressive encephalitis. The organism repli- 
cates within multinuclear giant cells and macrophages in 
the white matter [9], causing atrophy, water accumulation 
in the interstitium but no demyelination, inflammatory 
changes or focal destruction. 

The most common finding on CT or MRI is general- 
ized atrophy without focal abnormalities. Some degree of 
nonatrophic brain shrinkage is caused by systemic effects 
of the disease. In severe cases, diffuse symmetric hyper- 
intensity is seen in the supratentorial white matter, pre- 
dominantly in the periventricular region. Mass effect and 
enhancement are absent. On T1 -weighted images, the 
white matter appears almost normal or slightly hy- 
pointense. 

Progressive Multifocal Leukoencephalopathy 

Progressive multifocal leukoencephalopathy (PML) is 
caused by a papovavirus, the JC virus. This virus is ubiq- 
uitous in the adult population. It is present in lymph 
nodes and may reside in the kidneys. When a deep im- 
munodepression is present, usually with CD4 cells below 
100/mm^, the virus infects the myelin-producing oligo- 
dendrocytes, which results in severe demyelination with 



little inflammatory reaction. Patients complain of focal 
and progressive neurological impairment with motor or 
visual function loss or cerebellar syndrome. 
Demyelination starts at the subcortical white matter, in 
the U fibers. Areas of demyelination are seen as hy- 
pointense signal on T1 -weighted images, with high signal 
intensity on T2-weighted and FLAIR images, without 
mass effect or enhancement [5]. There is always a strong 
correlation between the symptoms and the location of the 
abnormalities on MRI. 

In the past, PML was inevitably fatal, with death oc- 
curring within 6-12 months of disease onset. The admin- 
istration of drugs developed to treat HIV, such as protease 
inhibitors, can stabilize the lesions produced by PML, 
probably by improving the function of the immune sys- 
tem. Additionally, the incidence of PML, around 5% be- 
fore the development of antiretroviral drugs, has dropped 
significantly [11]. 

Prion Diseases 

A group of CNS diseases called transmissible spongi- 
form encephalopathies (TSE) is characterized by spongi- 
form degeneration of neurons in the cortex and subcorti- 
cal nuclei. TSE have been known to be transmissible 
since the 1920s, when it was observed that humans in 
Borneo eating the brain of defeated warriors were affect- 
ed by a fatal dementia called kuru. Several human and 
animal diseases produce this distinctive pattern, includ- 
ing kuru, bovine spongiform encephalopathy (“mad cow 
disease”), scrapie (sheep). There are 4 forms of TSE ac- 
cording to the way of contamination: 

1. Creutzfeldt- Jakob disease (CJD), the most frequent 
(80%) form of TSE, has a spontaneous and sporadic 
origin. Although spontaneous, tissues from patients af- 
fected by CJD may transmit the disease to other hu- 
mans when injected or grafted. Patients with CJD usu- 
ally present late in life (>50 years of age) with rapid 
onset of dementia and myoclonic jerks [12]. Most pa- 
tients die within a year of the onset of symptoms. 

2. Heritable TSE affect families and are known as 
Gertsmann-Strausler disease and fatal familial insomnia. 

3. Iatrogenic TSE are of medical transmission, when pa- 
tients receive blood transfusions or are grafted with 
contaminated tissues (hypophysial extracts, dura 
mater, cornea) from infected donors 

4. CDJ variant (vCDJ) is believed to affect patients who 
have eaten meat from affected cows. The epidemic has 
affected mostly the United Kingdom with more than 
1000 cases and France with 4 cases since 1996. The 
epidemic is now stopped. 

This classification shows the role of an infectious 
agent which become pathogenic in particular genetic set- 
tings. Stanley Prusiner and others have partially elucidat- 
ed the origin of TSE [13]. Although still controversial, the 
transmissible agents are likely to be proteins called pri- 
ons. The normal protein (PrP^) becomes pathogenic when 




88 



V Dousset 



misfolded, thus becoming insoluble and resistant to heat 
(Prpres) pj.pres capable of inserting themselves into 
the cell membrane of neurons and inducing their own re- 
production. They produce the spongiform degeneration 
of the brain. 

MRI is becoming the technique of choice for diagnos- 
tic orientation. The earliest MRI signs are symmetric 
basal ganglia and cortical hyperintensities on FLAIR and 
diffusion- weighted images [14]. In the clinical setting, 
these signs are quite specific, although not constant. 
Most cases of Creutzfeldt-Jakob disease are bilateral and 
symmetric, but the disease may be unilateral. Infarct and 
Creutzfeldt-Jakob disease can be differentiated on a clin- 
ical basis in most cases. Bilateral hyperintensities of the 
basal ganglia may be seen in deep venous thrombosis, in 
acute exposure to toxic agents, and in some metabolic 
disorders. Usually the clinical setting is far different from 
CJD, making these diagnoses unlikely. 

vCJD shows a peculiar MRI sign with a high signal in- 
tensity in the pulvinar of the thalami [15]. This sign is 
however sometimes seen in cases of non-variant CDJ. 
Lately, atrophy and high signal intensities in white mat- 
ter are present on MRI studies. Electroencephalography 
may reveal the presence of triphasic waves that strongly 
suggest the disease. This sign is however of low sensitiv- 
ity. CSF may be normal or have increased protein con- 
centration. The 14-3-3 protein may be suggestively, al- 
though not specifically, high. The identification of PrP^®^ 
protein in different organs (e.g. lymphoid organs, amyg- 
dala) is necessary to confirm the diagnosis. 

Bacterial Infections 

Many bacteria enter the CNS via a hematogenous route, 
by contiguity from the paranasal sinuses, inner ear or 
middle ear, or through a traumatic or surgical opening in 
the dura [1]. The infection may affect one or several 
compartments of the brain at the same time: subdural 
(empyema) or CSF spaces (meningitis) and the brain 
parenchyma (encephalitis followed by a circumscribed 
abscess). Arteries, veins and perivascular Virchow-Robin 
spaces contribute to the spread of the bacteria from one 
compartment to another. Furthermore, acute or rapidly 
progressive thromboses of these vessels lead to addition- 
al abnormalities. The infection may also gain the surface 
of the endothelial wall, making the so-called distal my- 
cotic aneurysms that have a high risk of rupture. 

Staphylococcus and Streptococcus pneumoniae 
spread to the CNS either by a hematogenous route or via 
adjacent cranial structures. Meningococci follow a 
hematogenous way and produce acute meningitis with 
high risk of death. Koch’s bacilli causing tuberculosis 
(TB) usually are of hematogenous origin, leading to 
acute or subacute meningitis or brain abscess. TB af- 
fects many people in underdeveloped countries and pa- 
tients with AIDS worldwide. Nocardia affects immuno- 
compromised patients (with AIDS or other conditions) 



and causes in many cases brain abscesses, usually con- 
temporarily with chest infection. Listeria monocyto- 
genes may affect newborns or patients eating a large 
amount of bacteria in contaminated foods. The distribu- 
tion of L. monocytogenes is usually the meninges and 
the rhombencephalum (brain stem and cerebellum) [16]. 
In neonates, brain abscesses may also be due to urinary 
germs such as E. coli and Proteus. Tropheryma whip- 
pelii causing Whipple’s disease is a rare infection, usu- 
ally but not constantly encountered in patients with di- 
gestive malabsorption. Syphilis is becoming a rare 
cause of CNS infection. It produces mostly chronic 
meningitis and, in a few cases, granulomas have been 
described along the cranial nerves. Lyme disease is 
caused by Borrelia burgdorferi and usually produces an 
infectious and granulomatous involvement of the white 
matter resembling multiple sclerosis (MS). 

Clinical and Imaging Features 

Systemic signs of infection (e.g. fever and leukocytosis) 
may be present. Signs of CNS contamination include the 
following: neck stiffness and photophobia when 
meninges are affected, and seizures and focal deficit or 
cerebellar signs when the parenchyma is involved. 

Imaging features are a reflection of the host and are 
vary according to the type and location of the infection. 
Techniques such as FLAIR and diffusion- weighted imag- 
ing, including the calculation of apparent diffusion coef- 
ficient (ADC) maps, are now used routinely in the imag- 
ing of inflammatory CNS diseases. On diffusion-weight- 
ed images, purulent material is usually hyperintense and 
the decreased ADC shows the restriction of water motion 
[2, 17]. Conversely, necrotic tumor debris has variable 
and heterogeneous intensity and usually an increased 
ADC. There is of course some overlap, especially in par- 
asitic toxoplasmic abscesses or in punctured bacterial ab- 
scesses, which may show increased ADC. Although less 
routinely use4 MRS reveals the presence of amino acids 
from extracellular proteolysis and bacterial metabolism 
(e.g. fermentation products), including succinate, acetate, 
leucine, valine, and alanine that are not seen in necrotic 
neoplasms [2-4]. 

Bacterial Meningitis 

The diagnosis of bacterial meningitis is confirmed with 
lumbar puncture, and imaging does not play a primary 
role in the detection or treatment of this disorder. It is rec- 
ommended to treat the patients as early as possible with- 
out waiting for imaging results. CT may be used to ex- 
clude increased intracranial pressure prior to lumbar 
puncture only when there are clinical doubts. T2-weight- 
ed images are usually normal. FLAIR imaging may be 
helpful in the diagnosis of meningitis, if the clinical pre- 
sentation is not straightforward. FLAIR shows diffuse 
subarachnoid hyperintensity while the CSF in the ventri- 
cles is dark. Enhancement in the CSF space evokes gran- 




Infectious Diseases of the Central Nervous System 



89 



ulomatous diseases, described later. Tuberculous menin- 
gitis may be seen as an enhancement in the cisterna and 
along the sylvian fissures. 

Subdural Empyema 

Subdural empyemas produce an acute progressive syn- 
drome characterized by fever, leukocytosis and the rapid 
development of neurologic abnormalities (e.g. seizure and 
hemiparesis) [18]. Subdural empyemas may result from 
direct spread of infection from the paranasal sinuses or the 
middle ear; they may also be of hematogenous origin or 
subsequent to meningitis or cerebritis, through the venous 
structures. Retrograde venous thrombosis leads to cortical 
venous stasis with marked cortical swelling. 

A complete imaging study of the brain and cranial 
structures is necessary in case of subdural empyema. 
Subdural empyemas can be difficult to detect, particular- 
ly on nonenhanced CT images. The collection is typical- 
ly narrow. There is disproportionate mass effect, with dif- 
ftise swelling of the hemisphere adjacent to the collection 
[1]. The cortex may appear thickened because of venous 
stasis. There may be evidence of sinusitis or mastoiditis. 

On MR images, the subdural collection is more con- 
spicuous, in particular on FLAIR images where it appears 
hyperintense to adjacent brain. On diffusion-weighted im- 
ages, the content may appear bright and ADC values are 
low. MRS reveals the presence of amino acids. Contrast- 
enhanced CT and MRI reveal thin enhancement of the 
deep and superficial membranes of the subdural empyema. 

Brain Abscesses 

An abscess is the result of the host defense against bac- 
teria that initially produce diffuse cerebritis or encephali- 
tis. Macrophages produce a true collagenous capsule that 
marks the passage from cerebritis to the abscess phase. 
On CT, the capsule may appear with a slight increased 
density. Contrast enhancement with iodine contrast 
agents shows a regular ring appearance. The capsule 
made of fibrin and collagen has a typical appearance on 
MRI: low signal intensity on T2-weighted images and 
FLAIR, and ring enhancement with gadolinium. 
Additionally, on FLAIR and T2-weighted images, vaso- 
genic edema (hyperintensity in the subcortical white mat- 
ter) is present [19]. 

The central necrotic region is hyperintense on FLAIR 
images, and isointense to CSF on T2-weighted images. On 
diffusion imaging the center appears bright, which may be 
due to “T2 shine-through” effects. On ADC maps, the 
central necrotic material is hypointense, which confirms 
the restriction of water motion. In at least two circum- 
stances, the ADC may be increased: in toxoplasmic ab- 
scesses and in bacterial abscesses that have been punc- 
tured. Nevertheless, the decreased ADC values help to dif- 
ferentiate abscess from necrotic brain tumors or metas- 
tases that have increased ADC values. In brain abscesses, 
MRS with long repetition time (TR) sequences reveals the 



presence of amino acids that are the proteolytic break- 
down and fermentation products unique to bacterial in- 
fection. Enhancement persists for up to 8 months. 

A peculiar feature of brain abscesses observed on CT 
and MRI is a miliary pattern, which corresponds to innu- 
merable, small abscesses in the parenchyma. This radi- 
ographic pattern develops following the hematogenous 
spread of Koch’s bacillus i.e. Mycobacterium tubercolo- 
sis producing TB or nocardia. 

Mycotic Aneurysms 

Intracranial infectious aneurysms are important condi- 
tions that are not rare. They usually occur in patients with 
staphylococcal endocarditis and are called “mycotic” 
aneurysms [20]. They also develop in intravenous drug 
abusers [21]. Their imaging presentation is usually a 
small mass in the subarachnoid space near the cortex 
with strong enhancement. They may rupture, leading to 
subarachnoid hemorrhage with high risk of death. They 
also can be revealed by focal infarcts or seizures. Stroke 
may occur without infective aneurysms in patients with 
valve endocarditis [22]. Nonruptured aneurysms may dis- 
appear with antibiotic therapy. Ruptured and sometimes 
nonruptured aneurysms need endovascular treatment or 
surgical clipping. 

Parasitic Infections 

The most common parasites that infect the CNS are [23]: 

1. Taenia solium from undercooked pork, responsible for 
neurocysticercosis 

2. Taenia echinococcus granulosus from the dog, respon- 
sible for hydatid cysts 

3. Taenia echinococcus multilocularis from the fox 

4. Toxoplasma gondii that develops in the CNS of HIV- 
infected patients 

5. Toxocara canis and Toxocara cati that produce CNS 
manifestations in children 

6. Paragonimus, from infected crabs or crayfish 
Other parasitic infections, including sparganosis, 

trichinosis and amebiasis, may also develop or manifest 
in the CNS. 

The three taenia usually produce cystic lesions; symp- 
toms often arise only after the death of the parasite, when 
the host response occurs. Thus, the cystic wall is com- 
pletely different from the capsule of a brain abscess. The 
cystic wall has a parasitic origin (not from the host) and 
it is not detectable by the host immunologic system until 
the larva dies. However, the location of the cyst may be 
responsible for symptoms such as seizures, mass effect or 
CSF occlusion, before the death of the parasite. 

Cysticercosis 

The larvae of Taenia solium enter the intestinal wall and 
develop in the brain, subarachnoid space or ventricles 




90 



V Dousset 



[24], Once the scolex is established, it makes itself im- 
munologically invisible to the host and therefore incites 
no inflammatory reaction. Live cysts are isointense to 
CSF on all pulse sequences. No enhancement is seen 
within the cyst wall while the organism is alive. The 
scolex may be seen as a 2- to 4-mm mural nodule in the 
cyst wall. There is no associated edema [1]. 

When the organism dies, an inflammatory granuloma- 
tous response occurs. The clinical manifestations are 
seizures or focal deficits. The wall enhances, and there is 
associated vasogenic edema. The dead cyst commonly 
calcifies. Patients treated with praziquantel may develop 
acute symptoms because of the simultaneous death of all 
live cysts. Subarachnoid cysts may often produce sec- 
ondary obstructive hydrocephalus. 

Hydatid Cysts 

Human echinococcis occurs by accidental ingestion of 
contaminated dog feces. The disease is endemic. The 
most common sites of development in humans are the liv- 
er, lung and bone. Brain is affected in less than 5% of pa- 
tients. It is usually a single, unilocular and quite large 
cyst. When the cyst ruptures it produces an inflammato- 
ry reaction. 

Echinococcus multilocularis causes a rare parasitic in- 
fection that usually has a fatal outcome. The cysts are rec- 
ognized because they resemble a bunch of grapes. 

Toxoplasmosis 

Toxoplasma gondii is distributed worldwide and infects 
more than 500 million humans [25]. It does not cause in- 
tracranial infections in immunocompetent hosts and 
therefore was rarely seen prior to the onset of the AIDS 
epidemic. However, toxoplasmosis may infect the em- 
bryo, producing cerebral malformations and intracranial 
calcifications. 

Toxoplasmosis is the most common cerebral mass le- 
sion encountered in the HIV-positive patient [25]. This is 
the first diagnosis to consider when CNS manifestations 
occur with rapid progression in HIV-infected patients. 
The imaging appearance may be ubiquitous but antibiot- 
ic treatment is efficient. Thus, AIDS patients with rapid 
CNS manifestations should be treated for toxoplasmosis 
regardless of the imaging features. The diagnosis may be 
reconsidered if treatment is inefficient. With HAART 
treatment, the incidence of toxoplasmosis has dropped 
[11]. Now, toxoplasmosis is encountered in patients who 
ignore their viral status for HIV It is not rare that patients 
presenting inaugural seizures and several brain lesions 
are positive for HIV This diagnosis must be considered 
by the radiologist. 

Although grossly identical to an abscess, the lesion is 
not encapsulated, which accounts for the histologic clas- 
sification of encephalitis rather than abscess [1]. In the 
majority of cases, multiple mass lesions are present, and 
they may be located anywhere within the brain. 



The imaging findings at the beginning include a mass 
effect without or with slight, not well demarcated, con- 
trast enhancement. Lately, the enhancement is quite sim- 
ilar to an abscess, like a ring. The central necrosis is typ- 
ically hyperintense on FLAIR and T2-weighted images. 
Diffusion-weighted imaging reveals heterogeneous inten- 
sity and the ADC is usually increased. Hemorrhage is not 
present at the time of initial diagnosis. Signs of hemor- 
rhage appear when the patient is treated with antibiotics. 
High signal intensity from methemoglobin is seen on 
nonenhanced T1 -weighted images, leading to confirma- 
tion of the diagnosis in patients under treatment. 

In patients who are not improving with antibiotics, the 
diagnosis of toxoplasmosis must be reconsidered with the 
primary goal of differentiating toxoplasmosis from lym- 
phoma. Although it is rare, Ijmiphoma is the second most 
common cause of mass lesions in patients with AIDS 
[25]. Lymphoma lesions are usually single and located in 
the deep gray and white matters (basal ganglia and cor- 
pus callosum). Lymphoma is often hypointense on T2- 
weighted images. There is mild adjacent edema with a 
mass effect lower than expected. Enhancement is usually 
diffuse but may be of a ring appearance, especially when 
the lesion is superior to 3.5 cm. Single photon emission 
CT (SPECT) with radioactive thallium can be used to 
confirm the diagnosis of lymphoma prior to therapy. 
Inflammatory lesions, including toxoplasmosis, are neg- 
ative on SPECT, while lymphoma is positive. When the 
diagnosis cannot be established noninvasively, biopsy is 
necessary. Non-Hodgkin’s lymphoma type B is the most 
common. Its outcome is unfortunately fatal. 

Infections with Toxocara canis and Toxocara cati 

These parasites are dog and cat nematodes. Human in- 
fection occurs by accidental ingestion of their eggs 
passed from pet animals. The liver, lung and peritoneum 
are most frequently involved. They produce focal lesions 
in the white matter that spontaneously resolve. Vasculitis 
or ganulomas around the larvae may form in the 
parenchyma. 

Fungal Infections 

Fungal CNS infections are possible in susceptible popu- 
lations, such as immunocompromised patients with 
AIDS, patients with leukemia, diabetes mellitus or renal 
diseases, those under aggressive chemotherapy, and in- 
travenous drug abusers using unsterilized materials [26]. 
The most frequent fungal infections are cryptococcosis 
due to Cryptococcus neoformans, aspergillosis, mu- 
cormycosis, candidiasis and histoplasmosis. 

The patient with cryptoccocosis usually presents with 
meningoencephalitis [26]. The infection is fatal without 
appropriate treatment using amphotericin B. Lumbar 
puncture is the single most useful test. After infecting the 
CSF, the organisms may extend along the perforating ar- 




Infectious Diseases of the Central Nervous System 



91 



teries in the perivascular Virchow-Robin spaces. The sig- 
nal intensity is similar to that of the cerebrospinal fluid. 
Cerebral edema rarely occurs. 

Aspergillosis is relatively rare in the AIDS popula- 
tion, but is more common in patients under corticos- 
teroid therapy. The organisms invade the lung parenchy- 
ma and spread hematogenously. Aspergillus may also 
gain the CNS via direct spread from the paranasal si- 
nuses or orbits. Aspergillous abscesses have a non-spe- 
cific appearance. 

Most patients with mucormycosis are diabetic. The 
pathology of infection is similar to that of aspergillosis. 
Rhinocerebral mucormycosis is a common feature. 

Granulomatous Infections and 
Immunoreactive Diseases 

Granulomatous Infections 

Granulomas correspond to cellular mass with T cells, 
macrophages and histiocytes without liquefied necrotic 
debris. Caseous (“cheesy”) necrosis is typical of tubercu- 
lous granulomas. 

Granulomatous infections can result from diverse 
pathogens, including bacteria {Mycobacterium, 
Nocardia, Actinomyces, spirochetes), fungi {Aspergillus 
or Mucorales), and parasites. Sarcoidosis is an idiopath- 
ic granulomatous disease that most commonly affects 
young, otherwise healthy adult patients [27]. Most gran- 
ulomatous infections affect the meninges. The brain 
parenchyma may be involved, usually by the spread of the 
granuloma along the perivascular Virchow-Robin spaces. 
Inflammatory pseudotumor may also affect the cavernous 
sinuses, the orbits and rarely the hypophysial sellae. 

CT and MRI features of granulomatous meningitis are 
cisternal enhancement, usually following the vessel 
routes. Thus, contrast-enhanced images are critical in es- 
tablishing the diagnosis of granulomatous meningitis. 
Basal meningitis often leads to hydrocephalus. There is 
often compromise of the vascular system with secondary 
infarction or hemorrhage. The combination of hydro- 
cephalus and deep infarction in a young adult should 
therefore always raise the suspicion of granulomatous 
meningitis [1]. 

The differential diagnosis of granulomatous infectious 
meningitis is neoplastic carcinomatous meningitis [28]. It 
has a predilection for the retrocerebellar cisterns. 
Sarcoidosis has a predilection for the suprasellar cistern, 
often producing thickening of the pituitary stalk [27]. 
Enhancement along the course of the cranial nerves is 
characteristie of sarcoidosis but can also be seen in lym- 
phoma. 

Vasculitis 

Vasculitis may be the result of direct spread from the lep- 
tomeninges along the perivascular spaces or from direct 



invasion and growth within the vessel lumen. It also can 
be the result of an immune reaction at the endothelial lev- 
el without infectious agents. Infarcts occur in the deep 
gray matter or in the cortex. 

Acute Disseminated Encephalomyelitis 

Acute disseminated encephalomyelitis (ADEM) is an au- 
toimmune disorder that is similar to multiple sclerosis 
except that it is monophasic [29]. ADEM occurs with a 
latency of one to several weeks after viral exposure or 
vaccination. In most of the cases, multiple lesions are 
present at the same time in the white matter, affecting the 
gray matter in at least one-third of cases. The disease 
may produce multifocal demyelination similar to viral 
encephalitis or multiple sclerosis. Enhancement is in- 
constant, although frequent. In most cases the evolution 
is good with steroid therapy. Death is possible in the 
most severe cases. 



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IDKD 2004 



Cerebral Infections 

D. Mikulis 

University of Toronto, Toronto, Canada 



Introduction 

The broad categories of diseases that afflict human be- 
ings continue to evolve as do the methods used to detect 
and evaluate them. Although most of the infectious dis- 
eases that affect the brain remain the same, there are a 
number of unusual infections that have appeared. 
Infectious agents are opportunists and will take advan- 
tage of weaknesses in the immune system that appear un- 
der a variety of conditions. Medical advances have lead 
to treatments and therapies that compromise the immune 
system. How, and imder what setting, these defects in the 
immune system appear influences the type of organism 
that invades and how the host responds to it. 
Manipulation of the immune response in the setting of 
transplantation and the appearance of acquired immime 
deficiency syndrome (AIDS) are examples in which un- 
usual infections occur. 

Conventional magnetic resonance imaging (MRI) 
methods have become the mainstay for evaluation of 
cerebral infections. Fimctional MRI methods, such as dif- 
fusion imaging and proton spectroscopy, that look at spe- 
cific characteristics of the tissues have further improved 
this capability. In view of these considerations, the infor- 
mation provided here focuses on the broad categories of 
infectious diseases that affect the brain, including those 
infections that appear in the immunocompromised host. 
The contribution that diffusion imaging and magnetic 
resonance spectroscopy (MRS) offer are also discussed. 

Cerebral Abscess 

In the pre-antibiotic era, brain abscesses were most com- 
monly caused by direct extension from infected paranasal 
sinuses. Now, the most common source is blood-borne 
bacterial seeding originating from infections elsewhere in 
the body. The abscess initially begins as a region of cere- 
bral inflammation or cerebritis that progresses to form a 
pus-filled cavity with a fibro-glial capsule. The typical 
abscess has a relatively thin, smooth wall showing intense 
contrast enhancement on computed tomography (CT) or 



MRI. Edema in the adjacent white matter is common. 
The abscess wall can appear bright on T1 -weighted im- 
ages. This is thought to be the result of a T1 -shortening 
effect related to constituents in white cells [1]. The criti- 
cal imaging issue, however, revolves around the similari- 
ty that a brain abscess can have with neoplastic diseases, 
especially metastases. Both commonly show ring en- 
hancement following contrast medium administration. 
How then, can they be distinguished? In general, the en- 
hancing ring of an abscess is thin and quite smooth as op- 
posed to a neoplasm where some irregularity or nodular- 
ity is present. The deepest portion of the abscess wall that 
“points” to the ventricular system may be thinner than 
other portions of the rim. However, these features are not 
reliable as metastases can have “perfect” enhancing rims, 
and abscesses can often have irregular margins. 

Increases in diagnostic specificity can be gained 
through application of diffusion methods and MRS. 
Abscess cavities on MR diffusion imaging typically show 
restricted water movement similar to that seen with acute 
ischemic stroke. Although the reason for this restriction 
has not been established, it is tempting to assume that it 
is related to dead or dying white cells “absorbing” any 
available extracellular water, analogous to the proposed 
mechanism for ischemic neurons and glia in ischemic 
stroke. One caveat is that metastases composed of cells 
with high nuclear to cytoplasmic ratios or cells that pro- 
duce large amounts of proteinaceous material (mucin) 
can also have ring enhancement and restricted water 
movement. 

Perhaps the most important contribution that MRS has 
made in the diagnosis of cerebral diseases is the ability to 
detect bacteria by their metabolic signatures. Certain 
b 5 q)roducts of bacterial metabolism are not seen in mam- 
mals in spectroscopically significant concentrations. 
Proton MRS is capable of detecting some of these sub- 
stances such as succinate and acetate as imique peaks in 
the spectra. However, treatment with antibiotics prior to 
MRS may reduce these metabolites to undetectable lev- 
els. Amino acids, produced by proteases released by 
white cells as part of the inflammatory response, can al- 
so be detected using proton MRS (Table 1). This is rele- 




94 



D. Mikulis 



Table 1. Amino acid peaks on proton magnetic resonance spec- 
troscopy (MRS) and their resonant frequencies in parts per mil- 
lion (ppm) 



Metabolite 


Resonant frequency 
(ppm) 


Broad amino acid peak (valine, leucine, 
and isoleucine)^ 


0.9 


Alanine^ 


1.4 and 1.6, doublet 


Succinate 


2.4 


Acetate 


1.9 


Pyruvate 


2.4 



^ Shows phase reversal at echo time (TE) = 135 ms 
^ Shows phase reversal at TE = 135 ms; peak at 1.4 ppm overlaps 
with peak of lactate doublet; can be seen in meningiomas and in 
cases of demyelination 



vant since large amounts of amino acids are not seen in 
normal brain or in other disease processes. They are pre- 
sent even if antibiotics have been administered. 

The expected utility of MRS should therefore be quite 
high in screening patients suspected of having brain ab- 
scesses. However, in modern practice, most patients have 
already been started on antibiotic treatment by the time 
MRI is performed. In my experience, the presence of bac- 
terial metabolites in patients previously treated with an- 
tibiotics is null. My colleagues and I have also failed to 
consistently detect amino acids. From the practical point 
of view, these deficiencies coupled with the difficulty in 
acquiring adequate spectra in sick patients who are un- 
able to cooperate for long spectroscopic acquisitions have 
diminished the value of MRS. The promise of faster ac- 
quisitions through new multicoil parallel imaging tech- 
niques should improve the applicability of MRS in these 
patients. 

In spite of these issues, the value of MRS may ulti- 
mately be in the ability to monitor therapeutic effica- 
cy. Declines in acetate and pyruvate have been report- 
ed one week after aspiration and medical treatment in 
5 patients with bacterial abscesses. Furthermore, these 
declines correlated with positive responses to treat- 
ment [2]. Experience with MRS for the assessment of 
brain abscesses is at an early stage and additional 
prospective investigation with larger studies is needed. 
Information concerning the incidence and the effect of 
antibiotics on specific spectral peaks would be useful 
in determining the sensitivity and specificity of MRS 
in general. 

Tuberculoma and Tuberculous Abscess 

Tuberculoma by definition is a parenchymal infection in 
which granulomas are found, whereas a tuberculous ab- 
scess contains pus devoid of granulomas and caseation. 
Both may show ring enhancement. Tuberculomas usually 
have decreased T2 signal surrounded by T2-bright edema 
in the adjacent brain, whereas the tuberculous abscess is 
bright on T2-weighted images with a hypointense wall. 



There is some evidence that diffusion-weighted images 
and apparent diffusion coefficients (ADC) are normal in 
tuberculomas whereas restriction of water movement is 
seen in tuberculous abscesses [3]. MRS has shown that 
there are differences between bacterial and mycobacteri- 
al brain abscesses. Although both can have elevations in 
lipid and lactate, there is a conspicuous absence of the 
peaks indicated in Table 1 in mycobacterial infections [4]. 
Tuberculomas may also show an elevated lipid peak re- 
lated to caseation. 



Meningitis 

The diagnosis of bacterial meningitis is almost always 
based on clinical presentation that consists of high 
fever, signs of meningismus, and a rapidly decreasing 
level of consciousness. Imaging is usually performed to 
assess the status of the ventricles prior to lumbar punc- 
ture since hydrocephalus is a relative contraindication to 
this procedure. CT can show evidence of increased at- 
tenuation in the basal cisterns and sulci due to high con- 
centrations of inflammatory cells. This must not be con- 
fused with subarachnoid hemorrhage since both can 
show increased attenuation in the basal cisterns [5]. 
Vessels in the subarachnoid space can become directly 
involved in the inflammatory process with necrotizing 
panarteritis and septic thrombophlebitis causing is- 
chemic injury to the brain. In addition, the inflammato- 
ry process can extend directly into the brain resulting in 
meningoencephalitis. Hydrocephalus occurs in most pa- 
tients, resulting in increased intracranial pressure that 
further compromises blood flow. These secondary man- 
ifestations of the meningeal infection can be detected 
with diffusion imaging which shows the extent of acute 
cortical ischemic injury. However, direct infection caus- 
ing cerebritis can have a similar appearance with evi- 
dence of restricted water movement [6]. We have rarely 
performed MRI in the assessment of acute meningitis 
since all patients initially receive broad-spectrum an- 
tibiotics and imaging would not alter subsequent man- 
agement. 

Imaging does play a role in the detection and manage- 
ment of less fulminant forms of meningitis. Tuberculous 
meningitis, for example, can initially be quite indolent 
with patients presenting with headache and cranial neu- 
ropathies. Untreated, the disease can progress rather sud- 
denly with high mortality. Lumbar puncture may show no 
growth of the bacillus, but there is usually an elevation in 
the white cell count and protein level. Precontrast MRI 
can be normal although FLAIR images may show in- 
creased signal in the sulci when cerebrospinal fluid (CSF) 
protein is sufficiently elevated [7]. Gadolinium-enhanced 
acquisitions can show striking enhancement of the lep- 
tomeninges. Tuberculous pachymenigeal involvement 
can also occur [8]. 

Patients with immune deficiencies are also suscepti- 
ble to tuberculous meningitis, but in addition, fungal. 




Cerebral Infections 



95 



viral and treponemal forms of the disease must be con- 
sidered, including cryptococcal, varicella-zoster, cy- 
tomegalovirus, and neurosyphilis. Although these other 
agents can be associated with leptomeningeal enhance- 
ment [9, 10], tuberculous meningitis typically produces 
an intense diffuse or nodular pattern of enhancement in 
the basal cisterns. Meningeal enhancement is uncom- 
mon in viral meningitis with MRI giving normal results 
unless an encephalitic component develops with signal 
changes in the parenchyma. 

Encephalitis 

Encephalitis can be divided into two groups (Table 2). In 
the first group, the virus is transmitted to humans via an 
insect vector (e.g. ticks and mosquitoes). Viruses in the 
second group infect the brain primarily. Brain inflamma- 
tion can also occur as a complication of viral infections 
such as measles, mumps and chicken pox, or in autoim- 
mune disorders such as multiple sclerosis or Rasmussen’s 
encephalitis, but these diseases are not considered here. 
Although Creutzfeldt-Jacob disease (CJD) may not be in- 
fectious disease in the true sense, the behavior of this 
agent mimics an infection and is discussed. 

In view of the number of viruses that can infect the 
central nervous system (CNS), time and space limitations 
impose limits on the subsequent discussion. Emphasis is 
therefore placed on adult herpes encephalitis. However, 
in order to stay current, I draw from my own experience 
to discuss the recent outbreak of West Nile virus in North 
America. Viral infections that occur in immunodeficient 
individuals are discussed in a separate section. 



Table 2. Some agents causing encephalitis, by infectious route. 
Group 1 agents require an insect vector, while group 2 agents in- 
fect the brain directly 



Group 1. Arbovirus encephalitic agents: 

St. Louis encephalitis virus 

Japanese B virus 

Equine encephalomyelitis virus 

Russian spring-summer encephalitis virus 

Louping ill virus 

Powassan virus 

Colorado tick fever virus 

California encephalitis virus 

West Nile virus 

Group 2. Primary infective agents: 

Herpes simplex 
Cytomegalovirus 
Epstein-Barr virus 

JC virus (progressive multifocal leukoencephalopathy, 
PML) 

Rabies 

Human immunodeficiency virus (HIV), LAV/HTLV- 
III or AIDS virus 

Subacute sclerosing panencephalitis (from reactivation 
of latent measles virus) 



Herpes Simplex Virus 

Herpes simplex encephalitis is the most common spo- 
radic viral infection in the Western world [11]. The virus 
resides in the trigeminal ganglion and is usually benign 
except when it produces lesions in the oral mucosa. 
Rarely does the virus re-activate to produce encephalitis. 
In general terms, the disease should be considered in any 
patient presenting with acute mental status changes and 
parenchymal signal abnormalities in the temporal lobe. 
Clinical outcome depends on early recognition and insti- 
tution of antiviral treatment (e.g. acyclovir). Unilateral 
presentation is common. I have even observed redevelop- 
ment of the infection in the contralateral temporal lobe 
several months after successful treatment of the initial in- 
fection. 

CT in the early stages of the infection gives normal im- 
ages. MRI is capable of showing decreased T1 and in- 
creased T2 involving the mesial temporal lobes and insu- 
lar cortex. As the disease progresses, signal enhancement 
with gadolinium can develop and the lesions can become 
hemorrhagic. Diffusion imaging can show evidence of 
both increased and decreased water mobilities. The areas 
of the parenchyma with restricted water movement, pre- 
sumably representing cytotoxic edema, were often asso- 
ciated with lesions that had minimal T2 signal changes, 
while those areas that showed increased water movement, 
indicating vasogenic edema, had prominent increases in 
T2 signal [12]. 

Although not proven, there is some evidence that cy- 
totoxic edema is seen early in viral encephalitis, perhaps 
as a result of premorbid changes in the cell (swelling) as 
the virus takes over cellular machinery [13]. Vasogenic 
edema appears later as the cells rupture. Alternatively, in- 
fectious load may be the controlling factor. This concept 
is supported by findings observed in vitro when cells are 
infected with West Nile virus [14]. If the cells are ex- 
posed to a high infectious load, they become swollen and 
rupture due to high viral budding and to loss of mem- 
brane integrity. High mobility group 1 (HMGBl) protein, 
a proinflammatory cytokine, is then released into the ex- 
tracellular space. This protein is a proinflammatory cy- 
tokine that in vivo leads to inflammation and vasogenic 
edema. If the infectious load is low, delayed cell death 
occurs due to apoptosis. This model therefore supports a 
similar temporal pattern of cytotoxic edema followed by 
vasogenic edema. 

West Nile Virus 

Prior to 1999, West Nile virus (WNV) was confined to 
Africa, the Middle East, and Asia. The first North 
American cases occurred in New York in 1999. The first 
Canadian case was reported in Ontario in 2001 [15]. As 
of 2002, WNV had spread to 44 states across the US and 
to 5 Canadian provinces. In 2002, there were 4156 cases 
of West Nile virus reported to the Centers for Disease 
Control in Atlanta, with 284 fatalities. In 2003, there 




96 



D. Mikulis 



were 8912 cases with 211 deaths [16]. Spread to Europe 
is now becoming a significant concern [17], 

Fortunately, most WNV infections are mild with no 
clinical symptoms. Approximately 20% of cases have 
mild illness lasting 3-6 days and consisting of malaise, 
headache, anorexia, myalgia, nausea, vomiting, or rash. 
One in 150 cases develop severe neurological disease 
consisting of meningitis or encephalitis. 

Imaging reports of these severe cases are now becom- 
ing available. The type of CNS involvement is different 
from that seen with herpes. WNV tends to involve the 
brain stem, cerebellum, and thalami. CT images are fre- 
quently normal, however MRI shows increased T2 signal 
with evidence of swelling within these structures. As op- 
posed to herpes infection, the neocortex is not usually in- 
volved by 'VWV infection. Gadolinium enhancement is 
not usually present except in the setting of meningitis 
where leptomeningeal enhancement occurs. The spinal 
cord and cauda equina can also be affected. Some pa- 
tients present with myeloradiculopathy similar to that 
seen with Guillain-Barre syndrome. Enhancement of the 
pia along the spinal cord and cauda equina has been ob- 
served. Parenchymal signal changes can also occur with- 
in the spinal cord. Pathologic changes in the spinal cord 
resemble poliomyelitis [18]. My colleagues and I report- 
ed a case in which diffusion imaging during the early 
phase of the disease showed marked restriction of water 
movement in the pons at a time when conventional se- 
quences were normal. Later in the disease water diffusion 
became markedly increased in pons [13]. As suggested 
previously, this changing pattern of water diffusion may 
be a signature of viral brain infections, but much work 
needs to be done to confirm this. 

Little information is available concerning MRS and 
encephalitis. Acquiring diagnostic spectra from the tem- 
poral lobe, brain stem, cerebellum, and thalamus is chal- 
lenging due to shimming problems that arise from tissues 
near the skull base. This is made even more difficult in 
uncooperative patients. Spectral similarities with brain 
tumors, showing elevations in choline and reductions in 
V-acetylaspartic acid (NAA), have been reported [19]. 
However, there are no specific spectroscopic features di- 
agnostic of encephalitis. Clearly, much more work needs 
to be done in this area. 



Prion Diseases 

Scrapie, bovine spongiform encephalopathy, kuru, and 
CJD are examples of prion (from “proteinaceous” and “in- 
fectious”) diseases causing spongiform encephalopathy. 
Scrapie occurs in sheep and goats. Kuru is found in New 
Guinea tribes that practice cannibalism. Bovine spongi- 
form encephalopathy has been linked with variant 
Creutzfeldt-Jakob disease that occurs in humans. In addi- 
tion to the variant form, which is probably of greatest con- 
cern since it may be propagated through food (eating con- 
taminated beef), sporadic and familial forms also exist. 



These diseases have a common theme in that the re- 
sponsible agent is thought to be a misfolded prion protein 
that induces further misfolding of normal prion proteins 
into protease-resistant aggregates. These accumulate and 
cause progressive cerebral degeneration over a period of 
3-6 months leading to death. A viral etiology or carrier, 
however, has not been completely ruled out as the cause 
of this disease [20]. 

The most important neuropathological feature from 
the neuroimaging standpoint is cytoplasmic vacuolization 
which is most likely responsible for the decreases in wa- 
ter diffusion observed on MR diffusion imaging [21]. 
Ultrastucturally, the cytoplasmic vacuoles contain a pro- 
liferation of membranes in a “labyrinth-like manner” ex- 
plaining the restriction in water movement [22]. There is 
also extensive gliosis in areas of neuronal loss, explain- 
ing the elevations in T2 relaxation [23]. However, these 
theories may not be correct as there is evidence that T2 
and ADC signal abnormalities correlate with sites of ab- 
normal prion protein deposition and not the presence of 
vacuoles or gliosis [24]. T2 and ADC abnormalities do 
evolve as the disease progresses. It has been suggested 
that in the initial phase of the disease, signal behavior is 
influenced by vacuoles in intact neurons, with diffusion 
imaging more sensitive than T2-weighted or FLAIR 
imaging. Later in the disease, as neurons disappear and 
are replaced by gliotic tissue, ADC may normalize and 
T2 abnormalities gain prominence [25]. 

Many unanswered questions remain. For example, it is 
not known if imaging can be used to distinguish the dif- 
ferent types of prion diseases. In my experience, there are 
two different imaging patterns. The first is the more clas- 
sic pattern in which there is involvement of the striatum 
and thalamus (especially the pulvinar and dorsomedial 
nuclei). The second is a somewhat random involvement 
of the cortex. As we gain more experience with the dis- 
ease, we may find that the first pattern evolves into the 
second as the disease progresses. Table 3 summarizes the 



Table 3. Imaging findings observed in prion disease 



Imaging technique 


Observations 


T2-weighted and FLAIR MR 


Pattern 1 : Increased SI in 


imaging 


striatum and thalamus 
Pattern 2: Increased SI in 
cortex (patchy)^ 


Diffusion-weighted imaging 


Increased SI (may change 
with disease progression) 


Apparent diffusion coefficient 


Decreased (may change with 
disease progression) 


Post-gadolinium T1 -weighted 


No enhancement 


MR imaging 


Magnetic resonance 


Decreased NAA 


spectroscopy 


Brain morphology 


Atrophy develops as disease 
progresses 



^ Pattern 1 may evolve into or be coexistent with pattern 2 
SI, signal intensity; NAA, A^-acetylaspartate 




Cerebral Infections 



97 



imaging findings observed in prion disease. There are 
few MRS studies in patients with prion disease. It ap- 
pears that MRS can detect neuronal loss, showing areas 
of reduced NAA, but there are no specific metabolites 
unique to prion disease [26]. 

Parasites 

Parasites infecting the brain typically affect individuals 
living in the undeveloped world. Parasitic CNS diseases 
include cysticercosis, malaria, neuroschistosomiasis, 
paragonimiasis, angiostrongyliasis, hydatid disease, 
sparganosis, trypanosomiasis, and gnathostomiasis. 
Toxoplasma is also considered to be a parasite, but since 
it is infective in immunocompromised hosts it is therefore 
discussed in the subsequent section. Since most parasitic 
infections of the CNS are rarely seen clinically, they are 
not discussed. Cysticercosis, however, is seen frequently 
enough to merit attention. 

The larval stage of the pork tapeworm {Taenia solium) 
infects the human nervous system, causing neurocys- 
ticercosis. The larvae have a variable appearance on 
imaging depending on whether they are: (1) viable and 
not under attack by the host’s immune defenses, (2) un- 
der immune attack, or (3) dead. It must be kept in mind 
that the larvae can infect the parenchyma directly or can 
seed the CSF spaces including the ventricles, sulci and 
cisterns. The larvae typically form cysts with a central 
scolex. The cysts are very thin-walled with a small cen- 
tral solid component representing the scolex. I have even 
observed the scolex enhance following gadolinium ad- 
ministration, a finding that is difficult to explain since it 
infers that some connection with the host blood supply 
exists for the contrast agent to find its way to the parasite 
in the cyst. The cysts can be multiloculated especially in 
the subarachnoid space, resulting in a “racemose” ap- 
pearance. If present in strategic locations of the ventricu- 
lar system, obstructive hydrocephalus may ensue. Some 
ventricular cysts can even move into dependent locations 
based on head position. When the cysts are viable, the in- 
tracystic fluid matches CSF on CT and all MRI pulse se- 
quences although some cysts can have slightly different 
signal on MRI, especially on FLAIR sequences. No ad- 
jacent edema is seen. 

The average size of the cysts is 0.5-1. 0 cm in diame- 
ter but they can be much larger. When a host immune re- 
action is present (typically associated with seizures), the 
cyst wall thickens and enhances. There is edema in the 
adjacent parenchyma. When the immune response is sue- 
cessful, the cysts begin to disappear and nodular areas of 
enhancement remain. These areas eventually become 
densely calcified. 

The cysticerci in this intermediate phase can be diffi- 
cult to distinguish from other nodular enhancing lesions. 
They may also be hypointense on T2-weighted images. 
A soft tissue radiographic survey of the patient’s muscles 
may reveal calcified cysticercal lesions, indicating the 



correct diagnosis. Occasionally, even calcified lesions 
may show some adjacent edema and contrast enhance- 
ment, probably reflecting continued host reaction to 
residual larval antigens. Diffusion imaging does not play 
a significant role in establishing the presence of cys- 
ticerci since the diagnosis is predominantly based on 
morphological characteristics alone. MRS may play a 
significant role especially in the nodular form of the dis- 
ease when the etiology is uncertain, since elevations in 
alanine, succinate, acetate, and amino acids point to an 
infectious etiology [27, 28]. Since nodular cysticereous 
lesions can be hypointense on T2-weighted images and 
may appear virtually identical to tuberculomas. MRS 
should be helpful in distinguishing between these simi- 
lar lesions. 



Infections in Immunocompromised Patients 

Not only are immunocompromised patients prone to in- 
fections that are seen in normal hosts, but they also be- 
come infected quite commonly by agents that are easily 
controlled by the normal immune system. This section fo- 
cuses on two of the most common agents that infect the 
immunocompromised patient: toxoplasma and JC virus. 
Finally, eryptococcal infection, encephalitis, and neu- 
rosyphillis are addressed. 

Toxoplasma Infection 

These infections tend to present as enlarging irregular 
mass lesions with perilesional edema, variable signal 
characteristics, and variable contrast enhancement. They 
can be difficult to distinguish from lymphoma, a signifi- 
cant diagnostic consideration in immunocompromised 
individuals, although some evidence exists that ADC val- 
ues are higher than those seen with lymphomas but also 
tend to be lower than in normal brain [29]. Toxoplasma 
has a predilection for the basal ganglia; any mass seen to 
involve this structure in an immunoeompromised indi- 
vidual should be considered to represent toxoplasmosis 
until proven otherwise, since it is easily treatable and re- 
sponds to appropriate treatment. Multiple lesions are usu- 
ally present and involvement of the frontal and parietal 
lobes is common. As opposed to other infectious agents, 
no specific or unique metabolite peaks are present in tox- 
oplasma lesions. In fact, MRS is unable to distinguish be- 
tween lymphoma and toxoplasmosis. 

Progressive Multifocal Leukoencephalopathy 

PML is caused by JC virus infection of oligodendrocytes 
in the immunocompromised host and typieally involves 
only white matter structures. It has the appearance of a 
demyelinating lesion and is associated with little or no 
contrast enhancement except along the margins of the le- 
sion. It can involve white matter in the posterior fossa 
and, like multiple sclerosis (MS), has a predilection for 




98 



D. Mikulis 



the middle cerebellar peduncle. Both increased and de- 
creased water diffusion values have been seen in these le- 
sions. It has recently been suggested that ADC is reduced 
in early infections (indicating swelling of infected cells) 
and later reverses to increased values as cells are lost and 
gliosis develops [30]. Decreased ADC is also observed in 
the advancing edge of older lesions. Tissue injury tends 
to be more severe in patients with AIDS compared to oth- 
er immunocompromised patients, most likely because of 
co-existent injury from HIV MRS shows a decrease in 
NAA that is usually greater than that seen with HIV en- 
cephalopathy alone. Choline is frequently elevated [31]. 
No spectral peaks unique to this infection have been iden- 
tified with proton spectrosocopy. 

Cryptococcal Infection 

Cryptococcal infections occur in the form of meningitis 
or mass lesions (cryptococcomas) in the CSF spaces or 
brain parenchyma. The typical infection is that of 
meningitis with spread into the Virchow-Robin (VR) 
spaces at the base of the brain into the basal ganglia. 
The enlarged VR spaces show increased T1 and T2 re- 
laxations without contrast enhancement. However, en- 
hancement in the meninges and in cryptococcomas can 
occur. Secretion of an external polysaccharide capsule 
by these yeast-like organisms gives rise to large gelati- 
nous pseudocysts that form in the ventricular system or 
subarachnoid space. Surprisingly, there is a paucity of 
information concerning diffusion imaging and MRS in 
patients with these lesions. 

HIV Encephalitis 

HIV enters the CNS via infected macrophages that cross 
the blood-brain barrier (BBB). Direct neuronal infection, 
as seen in other viral encephalitides, is thought not to oc- 
cur, although this has not been entirely ruled out. Since 
there is initial preservation of neurons, CNS symptoms 
consisting of dementia are delayed. 

It has been proposed that the pathogenesis of demen- 
tia proceeds along noninflammatory and inflammatory 
pathways. In the noninflammatory pathway, infection of 
the microglia inhibits the supportive function of these 
cells. Inhibition of growth factor and impaired clearance 
of excitotoxic neurotransmitters lead to neuronal loss. 
In the inflammatory pathway, production of proinflam- 
matory cytokines and the ensuing inflammatory process 
injure neurons directly, leading to gliosis and brain at- 
rophy [32]. 

MRI findings include white matter lesions and gener- 
alized cerebral atrophy. MRS shows elevations in choline 
and myoinositol markers of glial proliferation. There is 
also a reduction in NAA, indicating neuronal loss. 
Diffusion imaging is generally non-contributory, al- 
though diffusion tensor analysis may provide informa- 
tion at a time when diffusion-weighted imaging (DWI) is 
normal. 



CMV Encephalitis 

Ependymitis with periventricular enhancement suggests 
infection with cytomegalovirus (CMV) but parenchymal 
lesions can also be seen. 

Neurosyphillis 

Neurosyphilis is typically a meningovascular disease pro- 
ducing meningeal inflammation as well as ischemic brain 
injury from vasculitis and vascular occlusion. The 
meninges may show enhancement following contrast 
medium administration. Occasionally meningeal granu- 
lomas or “gummas” can form. These gummas can rarely 
be seen in the parenchyma as enhancing nodules with in- 
creased T2 signal intensity surrounded by edema. 
Ischemic brain infarction can occur due to vascular com- 
promise by the inflammatory process. In fact, significant 
vascular narrowing can be seen at angiography. 

A form of encephalitic involvement that is becoming 
increasingly recognized mimics the appearance of herpes 
encephalitis, in which there is increased T2 signal and 
mild swelling of the mesial temporal lobes [33]. This em- 
phasizes the need to maintain an open mind concerning 
the differential diagnosis of temporal lobe infections. The 
classic progression of neurosyphilis from meningeal to 
cerebrovascular and to encephalitic phases over decades 
can be considerably foreshortened in immunocompro- 
mised patients. Diffusion imaging can help to establish 
evidence of acute ischemic injury to the brain parenchy- 
ma as a result of vascular compromise. The role of MRS 
is unclear as there are no published cases in this disease. 

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IDKD 2004 



Diseases of the Sella 

IF. Bonneville*, W. Kucharczyk^ 

' Hopital J. Minjoz, CHU Besan9on, France 
^ Medical Imaging, University of Toronto, Toronto, Canada 



Introduction 

Pituitary adenomas are by far the most common patholo- 
gy in the region of the sella turcica. Accordingly, a large 
part of this synopsis is devoted to them, while the re- 
mainder discusses other common lesions in this area. The 
emphasis is on imaging diagnosis and differential diag- 
nosis. 



Pituitary Adenomas 

Magnetic resonance imaging (MRI) is usually the only 
imaging method needed for the morphological investiga- 
tion of pituitary adenomas. Computed tomography (CT) 
is occasionally helpful to complement the MRI examina- 
tion for better delineation of the bony skull base, anatom- 
ic variants, calcification and osseous malformations. 
Classically, pituitary adenomas are divided into two cat- 
egories: microadenomas are less than 10 mm in diameter, 
and macroadenomas are over 10 mm in diameter. 
Occasionally the term “picoadenoma” is used to describe 
lesions smaller than 3 mm; these pose diagnostic prob- 
lems due to their small size. 

Clinically, microadenomas usually present with en- 
docrine dysfunction. Rarely they may be a serendipitous 
discovery. On T1 -weighted images, pituitary microade- 
nomas are usually hypointense compared to the unaffect- 
ed anterior pituitary gland, and round or oval in shape. In 
approximately 25% of cases, however, the adenoma is 
isointense on T1 -weighted images. Pituitary microadeno- 
mas can also cause high signal intensity on T1 -weighted 
images, probably due to internal hemorrhagic transfor- 
mation of all or parts of the adenoma, a rather frequent 
phenomenon in prolactinomas. On T2-weighted images, 
the signal intensity of microadenomas typically resem- 
bles that of the temporal lobe cortex, slightly hyperin- 
tense to that of the normal adenohypophysis, which is 
close to that of white matter. The signal intensity on T2- 
weighted images varies, in particular, with the type of en- 
docrine activity. The diagnosis of microadenomas is sim- 
ple when they demonstrate high intensity on T2 -weight- 



ed images, although this signal may only represent a part 
of the adenoma. Increased intensity on T2-weighted im- 
ages is found in over 80% of microprolactinomas. 
Conversely iso- or hypointensity on T2-weighted images 
occurs in two-thirds of all growth hormone-secreting mi- 
croadenomas. T2 -weighted images are particularly help- 
ful when looking for picoadenomas for which T1 -weight- 
ed images, and even gadolinium-enhanced sequences, are 
negative. When both the Tl- and T2-weighted images 
corroborate the diagnosis, which is the usual case with 
prolactinomas, gadolinium enhancement is unnecessary. 
On the contrary, when the diagnosis has not been estab- 
lished, enhanced imaging is mandatory. A half-dose of 
gadolinium-chelate (0.05 mmol/kg) is usually adequate. 
Contrast-enhanced images typically show a hypointense 
lesion surrounded by the intense enhancement of the nor- 
mal pituitary gland, but even the contrast-enhanced im- 
ages may be negative if the tumor is extremely small, the 
dose of gadolinium is too high, or the visualization win- 
dow is too large. Delayed images taken 30-40 minutes af- 
ter injection of contrast medium may show late enhance- 
ment of the adenoma. Dynamic images are useful in the 
diagnosis of adenomas secreting adrenocorticotrophic 
hormone (ACTH), or are used as a complementary in- 
vestigation when clinical signs are strongly evocative of 
a pituitary adenoma, but conventional MR images are not 
convincing. 

Pituitary macroadenomas are intrasellar masses with 
extrasellar extension, which is usually upwards into the 
suprasellar cistern or laterally into the cavernous sinus. It 
is important to delineate this extension in relation to the 
various surrounding anatomical structures, and whether 
the tumor is likely to be firm, cystic, necrotic or hemor- 
rhagic, based on its signal intensity and enhancement. 
Macroadenomas with suprasellar extension are often 
polycyclical in shape with one or two extensions into the 
suprasellar cistern. Macroadenoma signal intensity is of- 
ten inhomogeneous, particularly on T2-weighted images, 
with disseminated areas of hyperintensity reflecting cys- 
tic or necrotic portions of the adenoma. The adenomatous 
tissue usually enhances slightly after contrast medium in- 
jection, but the object of enhanced imaging is to visual- 




Diseases of the Sella 



101 



ize normal pituitary tissue. It usually forms a strongly en- 
hancing pseudocapsule around the adenoma: above it, be- 
hind it, rarely below or in front of it, and usually unilat- 
erally. The coronal section of the enhanced T1 -weighted 
image generally reveals a unilateral layer of normal pitu- 
itary tissue located between the adenoma and the ele- 
ments of the cavernous sinus, of crucial importance to 
neurosurgeons. The hyperintense posterior lobe is modi- 
fied: it appears either flattened or displaced and is well 
seen on the axial sections, or an ectopic hyperintensity is 
located within the pituitary stalk, which is compressed by 
the superior pole of the macroadenoma. The pituitary 
stalk is tipped laterally. When the suprasellar extension is 
large, the chiasm itself may be difficult to identify. In 
such cases, T2-weighted coronal sections help because 
the optic chiasm is clearly hypointense. After gadolinium 
injection, discrete meningeal enhancement is usually no- 
ticeable near the area where the meninges are in contact 
with the adenoma, and particularly so in the anterior part 
of the posterior cranial fossa, along with a possible dural 
tail, which has previously been described with menin- 
giomas. In our experience, the enhanced dura has no 
specificity whatsoever. 

Involvement of the cavernous sinus can modify the 
prognosis, but compression and invasion remain difficult 
to differentiate. The best sign of invasion is complete en- 
circling of the intracavemous carotid by the tumor. The 
diagnosis can practically be eliminated if it can be 
demonstrated that a strip of normal pituitary tissue lies 
between the tumor and the cavernous sinus. Large pitu- 
itary adenomas can apply pressure onto the cavernous si- 
nus and cause convex deformation of its external wall 
without necessarily involving it. 

Other Considerations: Gender, Age, Hormone 
Secretion, Pregnancy 

Prolactin-secreting microadenomas are common in 
young women. Some may spontaneously remain dormant 
over long periods. They do not develop after menopause. 
When prolactin-secreting adenomas are discovered in 
male patients, they have usually reached the stage of 
macroadenomas. This is probably due in part to the fact 
that clinical signs are less obvious in men than in women, 
and in part to the fact that their development is probably 
different. Cavernous sinus involvement is far from ex- 
ceptional. Pediatric pituitary adenomas are not only ex- 
ceptional but also potentially active. Prolactin-secreting 
adenomas can be responsible for late puberty. 

Prolactinomas are usually discovered at the stage of 
microadenomas owing to distinctive clinical signs found 
in young women, including amenorrhea, galactorrhea, 
and hyperprolactinemia (over 30 or 40 pg/1). Most of the 
time, the prolactinoma is hypointense on T1 -weighted 
images, while it is hyperintense on T2 -weighted images 
in 4 cases out of 5. This hypersignal may only be exhib- 
ited by a portion of the adenoma. Correlation between 



prolactin levels and adenoma size is usually good. 
However, given two prolactinomas of equal size, the hy- 
pointense tumor on T2-weighted images secretes more 
than its counterpart. Medical treatment based on 
bromocriptine decreases adenoma volume drastically. As 
a result, diagnosis becomes difficult. We strongly recom- 
mend MRI documentation before instituting the medical 
treatment. In some cases when prolactinomas are imaged 
long after medical treatment with bromocriptine is start- 
ed, peculiar scarred tissue can be seen, which is evocative 
of a former pituitary adenoma: it is due to the local re- 
modeling of the pituitary gland, forming a “V” on its su- 
perior aspect. 

While prolactinomas and growth hormone (GH)-se- 
creting adenomas are usually located laterally in the sel- 
la turcica, ACTH-secreting adenomas in Cushing’s dis- 
ease, usually smaller in size, are more often located in the 
midline. Because of the severe prognosis of this disease 
and the surgical possibilities, ACTH-secreting lesions re- 
quire the most detailed and exhaustive imaging. GH-se- 
creting adenomas have the unique characteristic of ex- 
hibiting hypointensity on T2-weighted images in two- 
thirds of cases. Spontaneous infarction or necrosis of 
GH-secreting adenomas is far from exceptional. Some 
cases of acromegaly that were detected late in the course 
of the disease exhibited an enlarged, partially empty sel- 
la turcica, lined with adenomatous tissue that proved dif- 
ficult to analyze. Medical treatment based on octreotride 
analogs (somatostatin) decreases the size of the adenoma 
by an average of 35% and brings the level of so- 
matomedin C back to normal in 50% of cases. It is use- 
ful before surgery. 

Macroadenomas can be nonfunctioning, but they can 
also be prolactin-secreting adenomas, gonadotrope ade- 
nomas, and growth hormone-secreting adenomas. The 
greater their size, the more heterogeneous they are, as ar- 
eas of cystic necrosis are caused by poor tumoral blood 
supply. Gonadotrope adenomas are often massive and 
have a strong tendency to recur. 

Hemorrhage occurs in all or parts of 20% of all pitu- 
itary adenomas, but it is usually occult. Pituitary 
apoplexy, with the usual headache, pseudomeningeal 
syndrome, cranial nerve paralysis and severe hypopitu- 
itarism, is generally caused by massive hemorrhage with- 
in a pituitary macroadenoma. Smaller scale hemorrhage 
occurs much more often, and can be seen within pituitary 
adenomas. Bromocriptine is held responsible, to a certain 
degree, for intratumoral hemorrhages in prolactinomas, 
although the phenomenon is sometimes revealed on MR 
images before the treatment has been instituted. 
Recurrent hemorrhage is possible, and can cause repeat- 
ed headaches. Intratumoral hemorrhages are revealed by 
hyperintensity on the T1 -weighted image, sometimes 
with a blood-fluid level in the mass. 

Normal pituitary tissue has a longer T1 in women dur- 
ing pregnancy. Normal pituitary tissue increases in height 
during pregnancy (0.08 mm per week, i.e. almost 3 mm 
during the whole pregnancy). Pituitary adenomas also in- 




102 



J.F. Bonneville, W. Kucharczyk 



crease in volume, especially prolactinomas. The increased 
volume of the prolactinoma is especially visible when 
medical treatment has been interrupted. Vision and tumor 
size should be closely monitored during this period. 

Postoperative Sella Turcica and Pituitary Gland 

The surgical cavity is often filled with packing material 
after transphenoidal resection of a pituitary adenoma. 
Surgicel is frequently used, and is impregnated with 
blood and secretions. The presence of packing material, 
secretions and periadenomatous adhesions usually keeps 
the cavity from collapsing in the days and weeks that fol- 
low surgery. Blood, secretions and packing material 
slowly involute over the following 2-3 months. Even af- 
ter a few months, fragments of blood-impregnated 
Surgicel can still be found in the surgical cavity. If the 
diaphragm of the sella turcica is torn in the course of 
surgery, fat or muscle implants are inserted by the sur- 
geon to prevent the occurrence of a cerebrospinal fluid 
fistula. Their resorption takes much longer. Implanted 
fat involutes slowly and may exhibit hyperintensity on 
the T1 -weighted image up to 2-3 years after surgery. 
Postoperative MRI 2-3 months after surgery is useful to 
monitor further development of a resected adenoma. An 
earlier MRI examination performed 48 hours after 
surgery checks for potential complications and may vi- 
sualize residual tumor, i.e. a mass of intensity identical 
to that of the adenoma before surgery that commonly oc- 
cupies a peripheral portion of the adenoma. This early 
investigation is extremely helpful to interpret the follow- 
up MR images. At this stage, the remaining normal pi- 
tuitary tissue can be characterized: it is usually asym- 
metrical, and a hyperintense area is frequently observed 
at the base of the deviated hypophyseal stalk, due to an 
ectopic collection of neurohypophyseal secretory vesi- 
cles. The 2-month follow-up MRI examination is essen- 
tial to check for residual tumor. Late follow-up MRI, af- 
ter 1-2 years or more, usually demonstrates adenoma re- 
currence as a rounded or convex mass that is isointense 
with the initial tumor. 



Craniopharyngioma 

Craniopharyngiomas are epithelial-derived neoplasms 
that occur exclusively in the region of the sella turcica 
and suprasellar cistern or in the third ventricle. 
Craniopharyngiomas account for approximately 3% of all 
intracranial tumors and show no gender predominance. 
Craniopharyngiomas are hormonally inactive lesions. 
They have a bimodal age distribution; more than half oc- 
cur in childhood or adolescence, with a peak incidence 
between 5 and 10 years of age; there is a second smaller 
peak in adults in the sixth decade. The tumors vary great- 
ly in size, from a few millimeters to several centimeters 
in diameter. The epicenter of most is in the suprasellar 



cistern. Infrequently, the lesions are entirely within the 
sella or in the third ventricle. Most discussions of cranio- 
pharyngiomas in the literature are confined to the most 
frequent form, the classic adamantinomatous type, but a 
distinct squamous or papillary type is becoming recog- 
nized with increasing frequency. The classic form of 
craniopharyngioma is the adamantinomatous type, which 
is the most frequently encountered form of the lesion. 
Typically, cases are identified as suprasellar masses dur- 
ing the first two decades of life. These children most of- 
ten present with symptoms and signs of increased in- 
tracranial pressure: headache, nausea, vomiting, and pa- 
pilledema. Visual disturbances due to compression of the 
optic apparatus are also frequent but difficult to detect in 
young children. Others present with pituitary hypofimc- 
tion because of compression of the pituitary gland, pitu- 
itary stalk, or hjq)othalamus. Occasionally, lesions rup- 
ture into the subarachnoid space and evoke a chemical 
meningitis. Rarely, adamantinomatous craniopharyn- 
giomas are found outside the suprasellar cistern, includ- 
ing the posterior fossa, pineal region, third ventricle, and 
nasal cavity. Adamantinomatous tumors are almost al- 
ways grossly cystic and usually have both solid and cys- 
tic components. Calcification is seen in the vast majority 
of these tumors. Extensive fibrosis and signs of inflam- 
mation are often found with these lesions, particularly 
when they are recurrent, so that they adhere to adjacent 
structures, including the vasculature at the base of the 
brain. Optic tract edema on T2-weighted images is a 
common associated finding that is not commonly seen 
with other suprasellar masses. The inflammatory and fi- 
brotic nature of the lesions makes recurrence a not un- 
common event, typically occurring within the first 5 
years after surgery. The most characteristic MRI finding 
is a suprasellar mass that is itself heterogeneous but con- 
tains a cystic component that is well defined, internally 
uniform, and hyperintense on both Tl- and T2-weighted 
images. The lesions often encase nearby cerebral vascu- 
lature. The solid portion, which is frequently partially cal- 
cified, is represented as the heterogeneous region. On 
rare occasions the cyst is absent and the solid component 
is completely calcified. These calcified types of tumors 
can be entirely overlooked on MRI unless close scrutiny 
is paid to subtle distortion of the normal suprasellar 
anatomy. Contrast medium administration causes a mod- 
erate degree of enhancement of the solid portion of the 
tumor, which otherwise may be difficult to see. 

Papillary craniopharyngiomas are typically found in 
the adult patient. These lesions are solid, without calci- 
fication, and often found within the third ventricle. 
Although surgery remains the definitive mode of thera- 
py for all craniopharyngiomas, papillary variants are en- 
capsulated and are readily separable from nearby struc- 
tures and adjacent brain, so they are generally thought 
to recur much less frequently than the adamantinoma- 
tous type. On pathologic examination, papillary lesions 
do not show the features characteristic of the adaman- 
tinomatous variant. In papillary lesions, there is exten- 




Diseases of the Sella 



103 



sive squamous differentiation. In distinction from their 
adamantinomatous counterpart, MRI shows papillary 
craniopharyngiomas as solid lesions. As noted previ- 
ously, they are often situated within the third ventricle. 
These lesions demonstrate a non-specific signal intensi- 
ty pattern, without the characteristic hyperintensity on 
T1 -weighted images of the cystic component of 
adamantinomatous tumors. Like all craniopharyn- 
giomas, papillary lesions typically enhance. 

Rathke’s Cleft Cyst 

Symptomatic cysts of Rathke’s cleft are much less fre- 
quent than craniopharyngiomas, although they are a 
common incidental finding at autopsy. In a recent eval- 
uation of 1000 nonselected autopsy specimens, 113 pi- 
tuitary glands (11.3%) harbored incidental Rathke’s 
cleft cysts. These cysts are predominantly intrasellar in 
location. Of incidental Rathke’s cysts larger than 2 mm 
in a large autopsy series, 89% were localized to the cen- 
ter of the gland, whereas the remaining 1 1% extended to 
show predominant lateral lesions. In that series, of all 
incidental pituitary lesions localized to the central part 
of the gland, 87% were Rathke’s cysts. Others may be 
centered in the suprasellar cistern, usually midline and 
anterior to the stalk. Rathke’s cysts are found in all age 
groups. They share a common origin with some cranio- 
pharyngiomas in that they are thought to originate from 
remnants of squamous epithelium from Rathke’s cleft. 
The cyst wall is composed of a single cell layer of 
columnar, cuboidal, or squamous epithelium on a base- 
ment membrane. The epithelium is often ciliated and 
may contain goblet cells. The cyst contents are typical- 
ly mucoid, less commonly filled with serous fluid or 
desquamated cellular debris. Calcification in the cyst 
wall is rare. 

Most Rathke’s cleft cysts are small, asymptomatic, and 
discovered only at autopsy. Symptoms occur if the cyst 
enlarges sufficiently to compress the pituitary gland or 
optic chiasm and rarely, secondary to hemorrhage. The 
cysts with mucoid fluid are indistinguishable from cystic 
craniopharyngiomas on MRI; both are hyperintense on 
Tl- and T2-weighted images. The serous cysts match the 
signal intensity of cerebrospinal fluid (CSF) and is the 
only subtype that has the typical imaging features of be- 
nign cysts. Those containing cellular debris pose the 
greatest difficulty in differential diagnosis for they re- 
semble solid nodules. The surgical approaches to Rathke’s 
cleft cyst and craniopharyngioma differ. Because of in- 
frequent postoperative recurrences, partial removal or as- 
piration is sufficient. Rathke’s cleft cysts do not typically 
enhance. However, occasionally there may be thin mar- 
ginal enhancement of the cyst wall. This feature can be 
used to advantage to separate these cysts from cranio- 
pharyngiomas in difficult cases. CT may reveal calcifi- 
cation, frequently found in craniopharyngiomas, helping 
to distinguish the mass from a Rathke’s cleft cyst. 



Meningioma 

Approximately 10% of meningiomas occur in the 
parasellar region. These tumors arise from a variety of lo- 
cations around the sella including the tuberculum sellae, 
clinoid processes, medial sphenoid wing, and cavernous 
sinus. Meningiomas are usually slow-growing lesions 
that present because of compression of vital structures. 
Patients may suffer visual loss because of ophthalmople- 
gia due to cranial nerve involvement, proptosis due to ve- 
nous congestion at the orbital apex, or compression of the 
optic nerves, chiasm, or optic tracts. Accurate differenti- 
ation between meningioma and pituitary adenoma is im- 
portant because meningioma requires craniotomy, where- 
as a trans-sphenoidal route is preferred for removing 
most pituitary macroadenomas. Meningiomas are most 
frequently isointense relative to gray matter on unen- 
hanced Tl -weighted sequences, and less commonly hy- 
pointense. Approximately 50% remain isointense on the 
T2-weighted sequence, whereas 40% are hyperintense. 
Since there is little image contrast to distinguish menin- 
giomas from brain parenchyma, indirect signs such as a 
mass effect, thickening of the dura, buckling of adjacent 
white matter, white matter edema, and hyperostosis are 
important diagnostic features. Other diagnostic signs in- 
clude visualization of a cleft of CSF separating the tumor 
from the brain (thus denoting that the tumor has an extra- 
axial location) and a clear separation of the tumor from 
the pituitary gland (thus indicating that the tiunor is not 
of pituitary gland origin). The latter sign is particularly 
well assessed on sagittal views of planum sphenoidale 
meningiomas. A peripheral black rim has been described 
on the edges of these meningiomas. This is thought to be 
related to surrounding veins. Hyperostosis and calcifica- 
tion are features that may be apparent on MRI but are bet- 
ter assessed with CT. Vascular encasement is not uncom- 
mon, particularly with meningiomas in the cavernous si- 
nus. The pattern of encasement is of diagnostic value. 
Meningiomas commonly constrict the lumen of the en- 
cased vessel. This is rare with other tumors. As on CT, the 
intravenous administration of contrast medium markedly 
improves the visualization of basal meningiomas. They 
enhance intensely and homogeneously, often with a trail- 
ing edge of thick surrounding dura (the “dural tail sign”). 

Chiasmatic and Hypothalamic Gliomas 

The distinction between chiasmatic and hypothalamic 
gliomas often depends on the predominant position of 
the lesion. In many cases the origin of large gliomas can- 
not be definitively determined as the hypothalamus and 
chiasm are inseparable; therefore, hypothalamic and chi- 
asmatic gliomas are discussed as a single entity. These 
tumors are for the most part tumors of childhood: 75% 
occur in the first decade of life. There is an equal preva- 
lence in males and females. There is a definite associa- 
tion of optic nerve and chiasmatic gliomas with neurofi- 




104 



J.F. Bonneville, W. Kucharczyk 



bromatosis, more so for tumors that arise from the optic 
nerve rather than from the chiasm or hypothalamus. 
Tumors of chiasmal origin are also more aggressive than 
those originating from the optic nerves and tend to in- 
vade the hypothalamus and floor of the third ventricle 
and cause hydrocephalus. Patients suffer from monocu- 
lar or binocular visual disturbances, hydrocephalus, or 
hypothalamic dysfunction. The appearance of the tumor 
depends on its position and direction of growth. It can be 
confined to either the chiasm or the hypothalamus; how- 
ever, because of its slow growth, the tumor has usually 
attained a considerable size by the time of presentation 
and the site of origin is frequently conjectural. Smaller 
nerve and chiasmal tumors are visually distinct from the 
hypothalamus and their site of origin is more clear-cut. 
From the point of view of differential diagnosis, these 
smaller tumors can be difficult to distinguish from optic 
neuritis, which can also cause optic nerve enlargement. 
The clinical history is important in these cases (neuritis 
is painful, tumor is not) and, if necessary, interval fol- 
low-up of neuritis will demonstrate resolution of optic 
nerve swelling. On T1 -weighted images, the tumors are 
most often isointense while on T2-weighted images they 
are moderately hyperintense. Calcification and hemor- 
rhage are not features of these gliomas but cysts are 
seen, particularly in the larger hypothalamic tumors. 
Contrast enhancement occurs in about half of all cases. 
Because of the tumor’s known propensity to invade the 
brain along the optic radiations, T2-weighted images of 
the entire brain are necessary. This pattern of tumor ex- 
tension is readily evident as hyperintensity on the T2- 
weighted image; however, patients with neurofibromato- 
sis (NF) present a problem in differential diagnosis. This 
relates to a high incidence of benign cerebral hamar- 
tomas and atypical glial cell rests in NF that can exactly 
mimic glioma. These both appear as areas of high signal 
intensity on T2-weighted images within the optic radia- 
tions. Lack of interval growth and possibly the absence 
of contrast enhancement are more supportive of a diag- 
nosis of hamartoma while enhancement suggests glioma. 

Metastases 

Symptomatic metastases to the pituitary gland are found 
in l%-5Vo of cancer patients. These are primarily patients 
with advanced, disseminated malignancy, particularly 
breast and bronchogenic carcinoma. The vast majority die 
of their underlying disease before becoming symptomatic 
of pituitary disease. Autopsy series have demonstrated a 
much higher incidence, but these by and large are small 
and asymptomatic lesions. Intrasellar and juxtasellar 
metastases arise via hematogenous seeding to the pitu- 
itary gland and stalk, by CSF seeding, and by direct ex- 
tension from head and neck neoplasms. There are no dis- 
tinctive MRI characteristics of metastases, although bone 
destruction is a prominent feature of lesions that involve 
skull base. 



Infections 

Infection in the suprasellar cistern and cavernous sinuses 
is usually part of a disseminated process, or occurs by 
means of intracranial extension of an extracranial infec- 
tion. The basal meninges in and around the suprasellar 
cistern are susceptible to tuberculous and other forms of 
granulomatous meningitis. The cistern may also be the 
site of parasitic cysts, in particular cysticercosis. In in- 
fections of the cavernous sinus, many of which are ac- 
companied by thrombophlebitis, the imaging findings on 
CT and MRI consist of a convex lateral contour to the af- 
fected cavernous sinus with evidence of a filling defect 
after contrast administration. The intracavernous portion 
of the internal carotid artery may also be narrowed sec- 
ondary to surrounding inflammatory change. Infections 
of the actual pituitary gland are uncommon. Direct viral 
infection of the hypophysis has never been established 
and bacterial infections are unusual. There has been spec- 
ulation that cases of acquired diabetes insipidus may be 
the result of a select viral infection of the hypothalamic 
supraoptic and paraventricular nuclei. Tuberculosis and 
syphilis, previously encountered in this region because of 
the higher general prevalence of these diseases in the 
population, are now rare. Gram-positive cocci are the 
most frequently identified organisms in pituitary ab- 
scesses. Pituitary abscesses usually occur in the presence 
of other sellar masses such as pituitary adenomas, 
Rathke’s cleft cysts, and craniopharyngiomas, indicating 
that these mass lesions function as predisposing factors to 
infection. There are a few reports on CT of pituitary ab- 
scesses. These indicate that the lesion is similar in ap- 
pearance to an adenoma. As a result of the frequent co- 
incidental occurrence of abscesses with adenomas, and 
because of their common clinical presentations, the cor- 
rect preoperative diagnosis of abscess is difficult and 
rarely made. Noncontrast MRI demonstrates a sellar 
mass indistinguishable from an adenoma. With intra- 
venous administration of contrast medium, there is rim 
enhancement of the mass with persistence of low intensi- 
ty in the center. 

Noninfectious Inflammatory Lesions 

Lymphocytic hypophysitis is a rare, noninfectious in- 
flammatory disorder of the pituitary gland. It occurs al- 
most exclusively in women and particularly during late 
pregnancy or in the post-partum period. The diagnosis 
should be considered in a female patient who is in the 
peripartum period with a pituitary mass, particularly 
when the degree of hypopituitarism is greater than that 
expected from the size of the mass. It is believed that, if 
untreated, the disease results in panhypopituitarism. 
Clinically the patient complains of headache, visual loss, 
failure to resume menses, inability to lactate, or some 
combination thereof. Pituitary hormone levels are de- 
pressed. CT and MRI demonstrate diffuse enlargement of 




Diseases of the Sella 



105 



the anterior lobe without evidence of any focal abnor- 
mality or change in internal characteristics of the gland. 
The distinction between simple pituitary h 5 T)erplasia and 
lymphocytic hypophysitis may be difficult on MRI alone, 
so clinical correlation is required in this setting. 

Sarcoid afflicting the hypothalamic-pituitary axis usu- 
ally manifests itself clinically as diabetes insipidus, or oc- 
casionally as a deficiency of one or more anterior lobe 
hormones. Low signal intensity on T2-weighted images is 
one finding that occurs in sarcoid with some frequency, 
but rarely in other diseases, with few exceptions (other 
granulomatous inflammatory diseases, lymphoma, some 
meningiomas). This low signal finding may aid in differ- 
ential diagnosis. Also, the presence of multiple, scattered 
intraparenchymal brain lesions should raise the possibil- 
ity of the diagnosis, as should diffuse or multifocal le- 
sions of the basal meninges. The latter are best defined 
on coronal contrast-enhanced T1 -weighted images. 

Tolosa-Hunt syndrome (THS) refers to a painful oph- 
thalmoplegia caused by an inflammatory lesion of the 
cavernous sinus that is responsive to steroid therapy. 
Pathologically, the process is similar to orbital pseudotu- 
mor. Imaging in this disorder is often normal, or may 
show subtle findings such as asymmetric enlargement of 
the cavernous sinus, enhancement of the prepontine cis- 
tern, or abnormal soft tissue density in the orbital apex. 
The lesion resolves promptly with steroid therapy. 
Hypointensity on T2-weighted images may be observed; 
since this observation is uncommon in all but a few oth- 
er diseases (e.g. meningioma, lymphoma, and sarcoid), 
it may be helpful in diagnosis. Clinical history allows 
further precision in differential diagnosis: meningioma 
does not respond to steroids while lymphoma and sar- 
coid have evidence of a primary disease elsewhere in al- 
most all cases. 



Vascular Lesions 

Saccular aneurysms in the sella turcica and parasellar 
area arise from either the cavernous sinus portion of the 
carotid artery or its supraclinoid segment. These are ex- 
tremely important lesions to identify correctly. Confusion 
with a solid tumor can lead to surgical catastrophes. 
Fortunately, their MRI appearance is distinctive and eas- 
ily appreciated. Aneurysms are well defined and lack any 
internal signal on spin echo (SE) images, the so-called 
signal void created by rapidly flowing blood. This blood 
flow may also cause substantial artifacts on the image, 
usually manifest as multiple ghosts in the phase-encoding 
direction, and in itself is a useful diagnostic sign. 
Thrombus in the aneurysm lumen fundamentally alters 
these characteristics, the clot usually appearing as multi- 
lamellated high signal on T1 -weighted SE images, par- 
tially or completely filling the lumen. Hemosiderin may 
be visible in the adjacent brain, evident as a rim of low 
signal intensity on T2-weighted SE images, or on gradi- 
ent echo (GE) images. If confusion exists as to the vas- 



cular nature of these lesions, MR angiography is used to 
confirm the diagnosis, define the neck of the aneurysm 
and establish the relationship of the aneurysm to the ma- 
jor vessels. 

Carotid cavernous fistulas are abnormal communica- 
tions between the carotid artery and cavernous sinus. 
Most cases are due to trauma; less frequently they are 
“spontaneous”. These spontaneous cases are due to a va- 
riety of abnormalities, including atherosclerotic degener- 
ation of the arterial wall, congenital defects in the media, 
or rupture of an internal carotid aneurysm within the cav- 
ernous sinus. Dural arteriovenous malformations (AVMs) 
of the cavernous sinus are another form of abnormal ar- 
teriovenous (AV) communication in this region. On MRI 
the dilatation of the venous structures, in particular the 
ophthalmic vein and cavernous sinus, is usually clearly 
visible. The intercavernous venous channels dilate in 
carotid cavernous fistulas and may also be seen on MR 
images. Furthermore, the internal character of the cav- 
ernous sinus is altered; definite flow channels become 
evident secondary to the arterial rates of flow within the 
sinus. The fistulous communication itself is most often 
occult on MRI. The pituitary gland has been noted to be 
prominent in cases of dural arteriovenous fistula without 
evidence of endocrine dysfunction. The exact mechanism 
of pituitary enlargement is not known, however venous 
congestion is a postulated cause. 

Cavernous hemangiomas are acquired lesions and not 
true malformations. However, there have been a few re- 
ports of extra-axial cavernous hemangiomas occurring in 
the suprasellar cistern. Of importance is that one of these 
hemangiomas did not have the features usually associat- 
ed with, and so highly characteristic of, cavernous he- 
mangiomas in the brain. The atypical appearance of ex- 
tra-axial cavernous hemangiomas indicates that some 
caution must be exercised in the differential diagnosis of 
parasellar masses, because even though cavernous he- 
mangiomas in this location are rare, failure of the surgeon 
to appreciate their vascular nature can lead to unantici- 
pated hemorrhage. Cavernous hemangiomas should at 
least be considered in the differential diagnosis of solid, 
suprasellar masses that do not have the classic features of 
more common lesions, in particular craniopharyngiomas 
or meningiomas. Furthermore, T2-weighted images 
should be a routine part of the MRI protocol for suprasel- 
lar masses because visualization of a peripheral dark rim 
may be the only sign of the nature of the lesion. 

Other Conditions 

Many other lesions may involve the sella turcica and 
parasellar region. These include mass lesions such as 
germinoma, epidermoid, dermoid, teratoma, schwanno- 
ma, chordoma, ecchordosis, choristoma, arachnoid cyst, 
hamartoma, and Langerhans cell histiocytosis. Also, 
there are several important metabolic conditions that 
may cause pituitary dysfunction or MRI-observable ab- 




106 

normalities in and around the sella. These include dia- 
betes insipidus, growth hormone deficiency, hemochro- 
matosis, hypermagnesemia and hypothyroidism. Space 
limitations preclude their further discussion in this syn- 
opsis. 

Suggested Reading 

Ahmadi J, Destian S, Apuzzo MLJ, Segall HD, Zee CS (1992) 
Cystic fluid in craniopharyngiomas: MR imaging and quanti- 
tative analysis. Radiology 1812:783-785 
Bonneville JF, Cattin F, Gorczyca W, Hardy J (1993) Pituitary mi- 
cro-adenomas: early enhancement with dynamic CT-implica- 
tions of arterial blood supply and potential importance. 
Radiology 187:857-861 

Colombo N, Loli P, Vignati F, Scialfa G (1994) MR of corti- 
cotropin-secreting pituitary microadenomas. AJNR Am J 
Neuroradiol 15:1591-1595 

Davis PC, Gokhale KA, Josep GJ (1983) Pituitary adenoma: cor- 
relation of half dose gadolinium enhanced MRI with surgical 
findings in 26 patients. Radiology 180:779-784 
Dietemann JL, Portha C, Cattin F, Mollet E, Bonneville JF (1983) 
CT follow-up of microprolactinomas during bromocriptine-in- 
duced pregnancy. Neuroradiology 25:133 
Doppman JL, Frank JA, Dwyer AJ et al (1988) Gadolinium DTPA 
enhanced MR imaging of ACTH-secreting microadenomas of 
the pituitary gland. J Comput Assist Tomogr 12:728-735 
Kucharczyk W, Bishop JE, Plewes DB et al (1993) Dynamic MR 
imaging of pituitary microadenomas with FSE T1 -weighted 
shared view MRI. SMRM Annual Meeting, New York 
Kucharczyk W, Bishop JE, Plewes DB, Keller MA, George S 
(1994) Detection of pituitary microadenomas: comparaison of 
dynamic keyhole fast spin-echo, unenhanced, and convention- 



J.F. Bonneville, W. Kucharczyk 

al contrast-enhanced MR imaging. AJNR Am J Neuroradiol 
163:671-679 

Kucharczyk W, Davis DO, Kelly WM, Sze G, Norman D, Newton 
TH (1986) Pituitary adenomas: high-resolution MR imaging at 
1.5 T. Radiology 161:761-765 

Kucharczyk W, Montanera WJ, Becker LE (1996) The sella turci- 
ca and parasellar region. In: Atlas SW (ed) Magnetic reso- 
nance imaging of the brain and spine, 2nd edn. Lippincott- 
Raven, Philadelphia 

Kucharczyk W, Peck WW, Kelly WM, Norman D, Newton TH 
(1987) Rathke cleft cysts: CT, MR imaging and pathologic fea- 
tures. Radiology 165:491-495 

Lundin P, Bergstrom K, Nyman R, Lundberg PO, Muhr C (1992) 
Macroprolactinomas: serial MR imaging in long term 
bromocriptine therapy. AJNR Am J Neuroradiol 13:1279-1291 

Lundin P (1997) Long-term octreotide therapy in growth hormone- 
secreting pituitary adenomas: evaluation with serial MR. 
AJNR Am J Neuroradiol 18:765-772 

Nagahata M, Hosoya T, Kayama T, Yamaguchi K (1998) Edema 
along the optic tract: a useful MR finding for the diagnosis of 
craniopharyngiomas. AJNR Am J Neuroradiol 19:1753-1757 

Naylor MF, Scheithauer BW, Forbes GS, Tomlinson FH, Young WF 
(1995) Rathke cleft cyst: CT, MR, and pathology of 23 cases. 
J Comput Assist Tomogr 19(6):853-859 

Oka H, Kawano N, Suwa T, Yada K, Kan S, Kameya T (1994) 
Radiological study of symptomatic Rathke ’s cleft cysts. 
Neurosurgery 35(4):632-636 

Steiner E, Knosp E, Herold CJ et al (1992) Pituitary adenomas: 
findings of postoperative MR imaging. Radiology 185:521-527 

Teramoto A, Hirakawa K, Sanno N, Osamura Y (1994) Incidental 
pituitary lesions in 1,000 unselected autopsy specimens. 
Radiology 193:161-164 

Voelker J, Campbell R, Muller J (1991) Clinical, radiographic, and 
pathological features of symptomatic Rathke ’s cleft cysts. J 
Neurosurgery 74:535-544 




IDKD 2004 



Neuroimaging Diagnosis of Primary Brain Neoplasms in Childhood 

W.S. Ball 

Imaging Research Center, Cincinnati Children’s Hospital Medical Center, and Department of Biomedical Engineering, University of 
Cincinnati, Cincinnati, OH, USA 



Introduction 

While not as frequent as in the adult population, prima- 
ry neoplasm of the brain still constitutes the most fre- 
quently encountered solid tumor arising in the pediatric 
age group [1,2]. Tumors may be encountered in all age 
groups during childhood [3]. Supratentorial tumors pre- 
dominate in the first year of life, whereas infratentorial 
tumors are more frequent in the age range of 1-8 years 
[3-5]. In the second decade of life, the proportions of in- 
fratentorial vs. supratentorial tumors are similar to what 
is encountered in the adult population, with a predomi- 
nance of tumors in the supratentorial space. In general, 
there is a tendency toward less aggressive glial tumors 
in children than in adults; however, primary brain tu- 
mors still account for significant morbidity and mortal- 
ity in the pediatric age group. More aggressive therapies 
have also had a greater negative impact on brain devel- 
opment especially when used in the first decade of life. 
Early diagnosis is still the key to aggressive manage- 
ment and outcome, and other than increased clinical 
surveillance, imaging plays the most important role of 
all of the laboratory modalities both in diagnosis and in 
follow-up. 

We generally divide primary brain neoplasms in 
children into two compartments; those arising in the in- 
fratentorial space and those involving the supratentori- 
al space. Further compartmentalization in the supraten- 
torial space includes those tumors involving the sella 
and suprasellar regions, those involving the pineal re- 
gion, tumors of the cerebral hemispheres and finally tu- 
mors of the cerebrospinal fluid (CSF) spaces and 
meninges. 

Infratentorial Neoplasms in Children 

The majority of childhood posterior fossa neoplasms [6- 
10] originate from brain parenchyma, arising from ei- 
ther brain stem or cerebellum. These are followed in fre- 
quency by tumors that are primarily intraventricular in 
origin, and then by extra-axial neoplasms originating 



from the surrounding leptomeninges, skull base, cranial 
nerves, or primitive embryonic rests of tissue. 
Histologically, gliomas, primarily consisting of astrocy- 
tomas of the brain stem and cerebellum and benign 
ependymomas, are the most common infratentorial tu- 
mors in the pediatric age group. These are followed in 
frequency by the primitive neuroectodermal tumors 
(PNET) of childhood (e.g. medulloblastoma, ependy- 
moblastoma, primary intracerebral neuroblastoma), tu- 
mors arising from the choroid plexus (e.g. papillomas, 
carcinomas), metastatic disease (e.g. lymphoma, 
leukemia, small cell tumors, sarcomas) and neoplasms 
arising from the region of the skull base (e.g. rhab- 
domyosarcoma, chordoma, chondrosarcoma). 

Since it is clear that magnetic resonance imaging 
(MRI) is the imaging modality of choice in the evaluation 
of infratentorial neoplasms in all ages of childhood, it is 
important for radiologists to be familiar with the general 
clinical signs and symptoms of their presentation in order 
to appropriately select MRI as the first examination. In 
children, the signs and symptoms of most infratentorial 
tumors depend on the site of origin and relationship to 
surrounding structures, the presence or absence of com- 
plications such as hydrocephalus and the extent of dis- 
ease. For example, a mass arising from the brain stem 
commonly presents with cranial neuropathies or motor 
deficits, but rarely obstructs the fourth ventricle, and on- 
ly as a late manifestation. Hydrocephalus is common, 
however, with intraventricular tumors such as ependymo- 
ma, choroid plexus papilloma/carcinoma or PNET. 

Brain Stem Glioma 

On computed tomography (CT) and MRI, brain stem 
gliomas are best identified according to alterations they 
produce in the size, shape, and density of the brain stem. 
Enlargement of the brain stem leads to compression of 
the surrounding cisterns including the perimesencephal- 
ic, prepontine, cerebellopontine, and circum-medullary 
cisternal CSF spaces. The fourth ventricle appears flat- 
tened, anterior to posterior, and is displaced posteriorly 
by the mass. Midbrain tumors commonly extend into the 




108 



W.S. Ball 



interpeduncular and posterior suprasellar cisterns, or will 
indent the inferior and posterior aspects of the third ven- 
tricle. Cervicomedullary tumors typically involve the 
medulla from the level of the pons to the upper or mid- 
dle cervical cord. Except when there is predominant ex- 
ophytic neoplasm, the brain stem appears expanded, but 
often maintains its ovoid shape. As a result of tethering 
of the basilar artery by short perforating arteries supply- 
ing the surface of the brain stem, anterior exophytic 
growth of the tumor will appear to envelop the basilar 
artery rather than displace this structure anteriorly. 
Despite what appears to be significant compression of the 
basilar artery by surrounding tumor, vertebrobasilar arte- 
rial insufficiency is quite rare. 

MRI is most useful in the detection of small brain 
stem gliomas, to determine the extent of the tumor, and 
to reveal the presence or absence of exophytic growth 
from a primary intra-axial tumor. In this capacity, there 
is considerably more benefit to performing MRI com- 
pared to CT. Sagittal T1 -weighted images are essential in 
defining the extent of the tumor, whereas axial sections 
permit the evaluation of tumor signal characteristics with 
the least interference from artifact. On T1 -weighted im- 
ages, tumor appears hypointense, rarely isointense, com- 
pared to the normal surrounding brain. The margins of 
the tumor, as they interface with surrounding CSF, are 
typically sharp; however, tumor margins with the brain 
stem or cerebellum are often irregular and poorly de- 
fined as the tumor infiltrates the normal surrounding 
brain. Despite its infiltrating nature, the bulk of the tu- 
mor remains relatively homogeneous. Most true tumor 
cysts, if present, are lower in signal on both Tl- and T2- 
weighted sequences than are solid portions of the tumor, 
but are typically higher in signal when compared to nor- 
mal CSF. Necrotic cysts may actually remain isointense 
on the Tl -weighted sections, but are hyperintense on T2- 
weighted images or enhance with gadolinium. On inter- 
mediate and T2-weighted images, the tumor is moder- 
ately to markedly hyperintense in signal, and remains 
relatively homogeneous in appearance. Tumor margins 
are better defined on T2-weighted images than on Tl- 
weighted sequences. Contrast enhancement with 
gadolinium is seen as frequently as that on CT with iod- 
inated contrast material. We have observed frequent en- 
hancement in exophytic tumor, compared to the en- 
hancement in the brain stem itself 

Cerebellar Astrocytomas 

On MRI, both solid and macrocystic tumors are easily 
identified on axial and coronal images as originating 
from the inferior and medial portions of the cerebellar 
hemisphere adjacent to the cerebellar tonsils, from the 
lateral cerebellar hemisphere, or from the vermis. The 
cyst contents appear low in signal intensity on Tl -weight- 
ed images except for the cyst margin which is typically 
isointense. The cyst fluid remains high in signal on Tl- 
weighted images when compared to CSF, due to its high- 



er protein content. Separation of cyst wall from sur- 
rounding brain may be difficult without the addition of 
contrast medium; however, in most cases, identification 
of the wall is easier with MRI than with CT. Mural nod- 
ules within the cyst wall often give it a lumpy, nodular or 
plaque-like appearance. Tumor nodules lying outside the 
cyst wall in surrounding brain parenchyma, however, are 
more difficult to recognize; they can appear mixed in sig- 
nal intensity (isointense and hypointense) on Tl -weight- 
ed images compared to normal cerebellum. On T2- 
weighted images, the cyst contents are hyperintense com- 
pared to CSF, also from their elevated protein content. 
Exophytic tumor outside the cyst wall may also appear 
mixed in signal intensity (hypointense and hyperintense) 
on T2-weighted images, whereas the bulk of tumor with- 
in the cyst wall is typically hyperintense. White matter 
tracts lying adjacent to the tumor appear hyperintense due 
to diffuse edema; this is a common finding in astrocy- 
tomas arising from the cerebellar hemisphere and vermis. 
Reactive edema in surrounding white matter is less com- 
mon with intraventricular neoplasms such as medul- 
loblastoma (PNET) or ependymoma, except when these 
tumors invade or infiltrate the cerebellar hemisphere. 

Predominantly solid cerebellar astrocytomas often 
contain small, more peripheral cysts, which have similar 
signal characteristics to the larger macrocyst. Solid tumor 
is usually slightly inhomogeneous in appearance, is isoin- 
tense or minimally hypointense on Tl -weighted images, 
and is moderately to markedly hyperintense on T2- 
weighted sequences. With the addition of contrast medi- 
um, both solid tumor and the rim of smaller cysts mod- 
erately enhance. On delayed images, contrast medium 
will often leach into the cyst itself, thus shortening its Tl 
relaxation over time. 

Primitive Neuroectodermal Tumors of Childhood 

Sagittal midline Tl -weighted images are important in de- 
termining the likely site of origin of the tumor. An indis- 
tinct interface of the tumor with the region of the inferi- 
or or superior medullary velum, combined with a rela- 
tively sharply defined margin with the brain stem and 
cerebellum, provide excellent clues as to the most likely 
site of tumor origin. The intraventricular extension of the 
tumor is easiest to identify in the sagittal projection as 
capping of the superior tumor surface by fourth ventricle. 

The appearance of the medulloblastoma on MRI is, in 
large part, due to the dense cellularity of the tumor. I be- 
lieve that MRI correlates better with the pathologic ap- 
pearance of this tumor, compared to CT. A typical ap- 
pearance for medulloblastoma on Tl -weighted images is 
that of a relatively homogeneous mass which is minimal- 
ly or moderately hypointense compared to cerebellar grey 
matter. On T2-weighted images, the tumor is only mini- 
mally to moderately hyperintense, and remains relatively 
homogeneous. Prominent vessels are common central to 
the tumor, appearing as serpiginous areas of signal void 
on T2-weighted spin echo or gradient acquisition images. 




Neuroimaging Diagnosis of Primary Brain Neoplasms in Childhood 



109 



A pattern such as this on MRI most closely correlates 
with the “classic” pattern on CT, but is frequently found 
with both CT patterns. Homogeneity on MRI correlates 
closely with the homogeneous histologic cellular charac- 
teristics of the tumor, despite a diverse cellular histology 
within the same tumor. 

Hemorrhage, calcification, and areas of necrosis can 
give this tumor an inhomogeneous appearance on MRI, 
which can be confused with ependymoma or cerebellar 
astrocytoma. Therefore, homogeneity alone cannot be 
used to indicate the diagnosis of a primitive neuroecto- 
dermal tumor. In my experience, heterogeneity in PNET 
most closely correlates with zones of ependymal or 
oligodendroglial differentiation in the tumor. 

Ependymoma 

The margins of the ependymal tumor are typically ill-de- 
fined and irregular. Tumor often originates or extends in- 
to the lateral recesses of the fourth ventricle, from where 
it may involve the cerebellopontine angle or grow 
through the foramen of Magendie into the cisterna 
magna. Minimal to moderate patchy enhancement is 
common, compared to the marked enhancement found in 
the cerebellar pilocytic astrocytoma or hemangioblas- 
toma. Solid ependymomas tend to enhance in a more 
nonuniform fashion; however, the pattern of enhance- 
ment alone is not a reliable sign to distinguish this tumor 
from other tumors involving the posterior fossa. 
Enhancement within the margin of necrosis may appear 
ring-like, and thus be confused with macrocystic rim en- 
hancement of an astrocytoma or an abscess. 

The intraventricular location of most ependymomas is 
best appreciated in the sagittal projection on T1 -weight- 
ed MR images, in which the fourth ventricle appears 
draped over the top of the mass. Due to its frequent ori- 
gin from the floor or lateral recesses of the fourth ventri- 
cle, the interface of tumor with the brain stem surface is 
often indistinct, whereas the interface of the mass with 
the inferior or superior medullary velum (the most fre- 
quent site of origin for medulloblastoma) remains dis- 
tinct. On T1 -weighted images, the tumor is typically in- 
homogeneous in signal, with areas that appear hypo-, iso-, 
or hyperintense. Hypointense regions most frequently 
represent cystic or necrotic degeneration within the tu- 
mor. Hyperintense signal is most commonly a result of 
hemorrhage within tumor parenchyma or true tumoral 
cysts. Heterogeneity on T2 -weighted images is also typi- 
cal of this tumor. Cystic regions appear especially hyper- 
intense on the second echo of a T2-weighted sequence. 
Solid tumor may be either isointense or minimally to 
moderately hyperintense in appearance on T2-weighted 
images. Areas of signal void within the tumor represent 
either calcification or prominent blood vessels draining 
this highly vascular neoplasm. The detection of calcifica- 
tion can be enhanced by the use of gradient acquisition 
imaging by taking advantage of the susceptibility effect 
produced by the calcium salts. 



Supratentorial Neoplasms 

Supratentorial neoplasms [11, 12] in children can be di- 
vided based on anatomic location into those involving the 
sella and suprasellar regions, the pineal region, the cere- 
bral hemispheres, and CSF spaces and meninges. 

Sellar and Suprasellar Regions 

The sella-suprasellar space is home for a variety of tu- 
mors such as astrocytoma (hypothalamic, optic pathway), 
craniopharyngioma, germinoma, adenoma, teratoma, epi- 
dermoid, hamartoma, histiocytoma, and metastases. 
Astrocytomas are most common, and arise either from 
the optic chiasm and optic nerves (optic pathway glioma) 
or from the floor of the third ventricle (hypothalamic 
glioma). The majority of these tumors are histologically 
benign, but lie in an unfavorable location. Because it is 
difficult to distinguish the two, they are often considered 
together. They are generally solid, enhance moderately, 
and appear hypointense on T1 -weighted and hyperintense 
on T2 -weighted images. Calcification and primary cysts 
are uncommon, but may appear following radiation ther- 
apy. Complications include hydrocephalus by obstructing 
the third and lateral ventricles, spontaneous hemorrhage 
and blindness. 

Craniopharyngiomas are benign tumors arising from 
remnants of Rathke’s pouch; 95%-98% involve the 
suprasellar cistern, 85% are cystic, and 85%-90% contain 
calcification. The appearance of the cyst on MRI depends 
on the relative amount of protein and keratin debris (hy- 
pointense on T1 -weighted images, hyperintense on T2- 
weighted images), hemorrhage (iso- or hyperintense on 
T1 -weighted images, hypo- or hyperintense on T2-weight- 
ed images) or cholesterol (hyperintense on T1 -weighted 
images, h}q)ointense on T2-weighted images) secreted by 
the wall into the cyst. Solid tumor is typically isointense on 
T1 -weighted images and only minimally hyperintense on 
the T2-weighted images. The cyst may become quit large 
and extend into the anterior or middle cranial fossa, or in- 
to the posterior fossa. CT is best at identifying calcifica- 
tion; however, similar results can be obtained using gradi- 
ent acquisition sequences with short repetition time (TR) 
and echo time (TE) and a small flip angle. 

Germinomas commonly present with diabetes in- 
sipidus. The clinical onset of the diabetes may actually 
precede the physical evidence of tumor by months. The 
tumor is a rapidly growing neoplasm that will invade the 
floor of the third ventricle, infundibulum and suprasellar 
cistern. The mass is typically slightly hypointense on Tl- 
weighted images, and isointense to minimally hyperin- 
tense on T2-weighted images. Marked enhancement is al- 
so a characteristic of this tumor. Germinomas are ex- 
tremely radiosensitive, such that a positive response to ra- 
diation therapy is virtually diagnostic of this disorder. 
Imaging cannot differentiate benign from malignant tu- 
mors within this heterogeneous group. 




110 



W.S. Ball 



Pineal Region 

Tumors of the pineal region include astrocytomas of the 
midbrain and surrounding cortex, PNETs (pinealoblas- 
toma), tumors of pineal cell origin, germ cell tumors, and 
tumors of neural origin (ganglioglioma). Tumors arising 
in the posterior aspect of the third ventricle (choroid 
plexus tumors, papillary ependymomas) can sometimes 
be confused with an extra-axial tumor in the pineal re- 
gion, posterior to the third ventricle. Midbrain astrocy- 
tomas may be solid or cystic (20%-30%), and may be 
calcified (30%). They are generally slow-growing tumors 
that frequently obstruct the posterior third ventricle. A 
small tectal ‘‘glioma” may be confused with primary 
stenosis of the aqueduct of Sylvius, especially when there 
is a late onset of presentation. Tectal gliomas are actual- 
ly low-grade gliomas or hamartomas with a slow growth 
potential that may or may not be associated with neu- 
rofibromatosis (NF)-l. Appropriate therapy is to treat the 
hydrocephalus, and simply follow this lesion for evidence 
of growth. 

PNETs of the pineal region are common in young chil- 
dren. They are predominantly solid, but may contain a 
cystic component that is often hemorrhagic. Signal char- 
acteristics vary considerably, however the solid tumor is 
usually isointense on T1 -weighted images and minimally 
to moderately hyperintense on T2-weighted images. 
Enhancement is common. The classic association of bi- 
lateral retinoblastomas with a mass in the pineal region 
(trilateral retinoblastoma) represents a secondary locus 
for PNET (pinealoblastoma). Germinomas and teratomas 
in the pineal region can appear similar to those located in 
the suprasellar region. 

Both ependymomas and choroid plexus neoplasms 
may arise in the posterior aspect of the third ventricle. In 
this location they may be confused with an extra-axial le- 
sion arising from the pineal region, or an intra-axial le- 
sion arising from the midbrain. Both generally appear as 
inhomogeneous irregular masses that are hypointense or 
isointense on T1 -weighted images and only minimally to 
moderately hyperintense on T2-weighted images. In gen- 
eral, the anterior interface of a pineal region mass will re- 
main distinct as it pushes the posterior wall of the third 
ventricle forward, whereas the anterior surface of the 
third ventricular tumor is usually irregular as it grows un- 
restrained into the ventricular lumen. 

Cerebral Hemispheres 

The incidence of cerebral hemispheric tumors in children 
is less than that found in adults. Low-grade tumors are 
more common among childhood hemispheric gliomas, 
whereas higher grade malignancies predominate in 
adults. Childhood hemispheric gliomas include astrocy- 
tomas, oligodendrogliomas and ependymomas. 
Additional hemispheric tumors in children are PNETs, 
neural tumors (ganglioglioma, gangliocytoma), and intra- 
parenchymal meningiomas or menigosarcomas. The ap- 



pearance of most astrocytomas in children is similar to 
that in adults, with the exception of pilocytic astrocy- 
tomas that are often cystic and well defined and that en- 
hance intensely compared to low-grade tumors in adults. 
Grade three or four astrocytomas and glioblastoma mul- 
tiforme appear similar in children to their adult counter- 
parts. The childhood oligodendroglioma also differs 
somewhat in appearance from its adult counterpart. In 
children, these tumors are generally benign, large and he- 
morrhagic, contain dense lamellar calcifications, and are 
often associated with a prominent cyst. Their appearance 
on MRI is generally that of a heterogeneous tumor with 
mixed signal characteristics on both Tl- and T2-weight- 
ed images. 

Gangliogliomas have a propensity for the middle cra- 
nial fossa and posterior deep parietal lobe. They appear 
as inhomogeneous solid masses with dense calcification, 
minimal enhancement, and indistinct margins. Unlike the 
oligodendroglioma, they generally lack a cystic compo- 
nent. The more cellular gangliocytoma can be difficult to 
diagnose and to see on imaging. As described by Altman 
[11], the lesion is hyperdense on CT and does not en- 
hance. On MRI, the lesions are best seen on Tl -weight- 
ed images or with the first echo of T2-weighted images 
as having mixed signal, and may disappear or actually de- 
crease in signal on the second echo of T2-weighted im- 
ages. 

CSF Spaces and Meninges 

Extra-axial tumors in children comprise meningiomas, 
meningosarcomas, primary bone tumors, and metastases, 
often from small round cell tumors such as neuroblas- 
toma. Childhood meningiomas have a high incidence for 
intraparenchymal involvement compared to those in 
adults. These lesions are typically isointense on Tl- 
weighted images and low in signal on T2-weighted im- 
ages. Enhancement is moderate to marked. Metastatic tu- 
mors with extra-axial involvement (e.g. neuroblastoma, 
Ewing’s sarcoma) typically include adjacent bony ero- 
sion, which must be carefully sought for on CT with bone 
windows. Intraventricular tumors may arise from a vari- 
ety of structures and represent several different histolo- 
gies. Most common are the tumors arising' from the 
choroid plexus, which represent either papillomas or car- 
cinomas, or have mixed histology for both. These are the 
most common intraventricular tumor to be encountered in 
the first several years of life. These tumors may result in 
hydrocephalus, which at times may be severe. The etiol- 
ogy of the hydrocephalus may be secondary to overpro- 
duction of CSF by a papillomatous tumor, but is most of- 
ten obstructive in nature. These tumors are typically 
isointense to hyperintense on Tl -weighted images, and 
are often isointense or even hypointense on T2-weighted 
images. Enhancement is common and is typically 
marked. Imaging differentiation of papilloma from carci- 
noma is generally not possible, as these tumors are often 
histologically mixed [9]. Other intraventricular tumors 




Neuroimaging Diagnosis of Primary Brain Neoplasms in Childhood 



111 



arising in childhood include ependymoma, meningioma, 
oligodendroglioma and astrocytoma. This group of intra- 
ventricular tumors typically arise in the older age group 
of 5-18 years of age. All tend to have similar appear- 
ances, and also resemble the papilloma-carcinoma mak- 
ing a specific imaging diagnosis difficult. 



References 

1. Naidich TP, Zimmerman RA (1984) Primary brain tumors in 
children. Semin Reontgenol 19(2): 100 

2. Schoenberg BS, Schoenberg DC, Christine BW et al (1976) 
The epidemiology of primary intracranial neoplasms of child- 
hood. Mayo Clin Proc 51:51 

3. Childhood Brain Tumor Consortium (1988) A study of child- 
hood brain tumors based on surgical biopsies from ten North 
American institutions: sample description. J Neurooncol 6:9-21 

4. Rorke LB, Schut L (1989) Introductory survey of pediatric 
brain tumors. In: McLaurin RL, Schut L, Venes JL, Epstein F 
(eds) Pediatric neurosurgery: surgery of the developing ner- 



vous system. WB Saunders, Philadelphia, pp 335-337 

5. Ambrosino MM, Hernanz-Schulmann M, Genieser NB, 
Wisoff J, Epstein F (1988) Brain tumors in infants less than a 
year of age. Pediatr Radiol 19:6-8 

6. Segal FID, Zee CS, Naidich TP et al (1982) Computed tomog- 
raphy of neoplasms of the posterior fossa in children. Radiol 
Clin North Am 20:23 

7. Gusnard D (1990) Cerebellar neoplasms in children. Semin 
Roentgenol 25:264-278 

8. Lee BCP, Kneeland JB, Walker RW et al (1985) MR imaging 
of brain stem tumors. Am J Neuroradiol 6:159-163 

9. Vasquez E, Ball WS, Prenger EC, Castellote A, Crone KR 
(1992) Magnetic resonance imaging of fourth ventricular 
choroid plexus neoplasms in childhood: a report of two cases. 
Pediatr Neurosurg 17:48-52 

10. Ball WS (1997) Infratentorial tumors. In Ball WS (ed) Pediatric 
neuroradiology. Lippincott-Raven, Philadelphia, pp ??? 

11. Altman NR (1988) MR and CT characteristics of gangliocy- 
tomas: a rare cause of epilepsy in children. AJNR Am J 
Neuroradiol 9:917 

12. Jones B, Patterson R (1997) Supratentorial feoplasms. In: Ball 
WS (ed) Pediatric neuroradiology. Lippincott-Raven, 
Philadelphia, pp ??? 




IDKD 2004 



Central Nervous System Diseases in Children 

C. Raybaud 

CHU Timone, Universite de la Mediterranee, Marseille, France 



Introduction 

Central nervous system (CNS) diseases in ehildren are 
significantly different from those in adults. They are re- 
lated to age-specific processes (e.g. hypoxic-ischaemic 
encephalopathies), pathologies (e.g. acute encephalo- 
myelitis), maturation (e.g. age-related epileptic syn- 
dromes, age-specific tumours), developmental processes 
(e.g. brain malformations) and genetic disorders (e.g. 
metabolic diseases). Technically, at least in very young 
children, the conditions of investigation - mostly with 
magnetic resonance imaging (MRI) - are quite different 
also. This paper provides an overview of what is specific 
to children in the way of investigating CNS diseases. 

Imaging Tools 

Ultrasonography (US) is the simplest tool for investigat- 
ing infants at the bedside. NeuroUS, however, has its own 
constraints: there are no acoustic windows in the spine of 
newborn infants after a few days nor in the skull of infants 
older than a few months. On the other hand, US can be 
used in utero for satisfactory depiction of brain and spine 
as early as the third month of gestation. Limitations of US 
are its relative lack of definition and specificity. Trans- 
cranial Doppler sonography may be used after the closure 
of the sutures in the same conditions as in adults; the tech- 
nique has a specific role in cases of sickle cell disease. 

Computed tomography (CT) is still useful, not only for 
evaluating the craniospinal skeleton, but also the brain. Its 
sensitivity is not as good as that of MRI, but it has con- 
siderably improved over the years. Its environment is sim- 
pler, volume acquisition is possible, and sedation is rarely 
needed anymore. In some pathologies, CNS examination 
may be part of a more general body study. Since ionizing 
radiation has potential noxious effects, especially in in- 
fants, CT should be limited to reasonable indications. 

Magnetic resonance imaging (MRI) has neuropaedi- 
atric peculiarities. Of course, it has unequalled anatomi- 
cal definition, sensitivity to tissue alterations and speci- 
ficity (even with conventional sequenees). A single ma- 



chine provides conventional imaging, water imaging (dif- 
fusion), chemical imaging (MR spectroscopy), function- 
al imaging (fMRI), vascular imaging (perfusion, MR an- 
giography) and tractography (DTI), in a way compatible 
with integrated data post-processing (morphometry, sig- 
nal averaging, multimodality integration, stereotactic sur- 
gical neuronavigation, etc.). 

Imaging sequences should be adapted to the maturing 
brain. The repetition time (TR) of a conventional spin 
eeho (SE) sequence has to be three-times longer than the 
Tl, which at 1.0-1. 5 T is about 700 ms in adults but 3000 
ms in neonates (personal data). A TR close to 10 000 ms 
is acceptable only with fast SE sequences, which on the 
other hand “look” more mature than the conventional SE 
images. In neonates, FLAIR images (T2 images with the 
free water signal cancelled) show a low white matter sig- 
nal because the white matter is composed of 90% water. 
Then as myelin precursors accumulate, the signal looks 
more like that of conventional T2 images, but the adult 
pattern is not reached before 3-4 years of age (compared 
to 2 years on conventional T2-weighted images). 

MRI has no known noxious effect on the maturing or- 
ganism, even foetal. But beeause of the acquisition times, 
full eooperation of the child is needed. In very small in- 
fants, feeding and simple contention are usually enough. 
In young or uncooperative ehildren, sedation or anaesthe- 
sia is necessary and, therefore, MRI is not completely 
noninvasive. Simple sedation, whiehever drug is used, 
needs experienced radiologists and nursing personnel and 
specific care (for monitoring, temperature, freedom of air- 
ways) before, during and after the procedure. The sensi- 
tive environment of MRI (high magnetic field, radiofre- 
quencies) makes things more difficult for neonates; MRI- 
compatible incubators have been recently developed. 

Conventional digital angiography still has indications 
in paediatric neuroradiology, for optimal visualization of 
the vascular tree (in cases of vasculitis, thrombophlebitis, 
arteriovenous malformations) and for endovascular treat- 
ments. 

Conventional myelography or CT myelography may be 
considered when the morphology of the spine or the pres- 
ence of metals makes MRI useless or impossible. 




113 



Central Nervous System Diseases in Children 

Imaging Strategies 

Detailed Imaging of the Foetal CNS 

There is no clinical expression of foetal CNS disease. 
Progression of pregnancy can be watched routinely with 
US from the early foetal period to term. CT is avoided be- 
cause of the noxious effect of X-rays. MRI complements 
the US data in three main instances: abnormal familial 
context (potential genetic disorder), abnormal mater- 
nofoetal context (abnormal pregnancy, infection, anoxia) 
and abnormal foetal context (abnormal US screening). 
MRI is not performed before weeks 17-18 of gestation 
because of the small size of the brain. At 20 weeks (mid- 
pregnancy), the brain is essentially complete as neuronal 
migration is achieved. Further growth is due to the mul- 
tiplication of the fibers, with their supporting astroglia 
and myelination. The changes in morphology of the brain 
(sulci and gyri) and the ongoing maturation (proceeding 
radiologically for at least two more years) are precisely 
timed. In the foetus, the normal layered pattern of the 
cerebral mantle, usually not apparent at US, is well 
demonstrated on MRI; from inside out, these layers are 
the periventricular germinal matrix, an intermediate glial 
cell layer (until week 28), the transient sub-plate (until 
birth), and the cortical ribbon. The pericerebral cere- 
brospinal fluid (CSF) space is prominent until week 32. 
The ventricular trigone measures 7-8 mm, and should not 
be larger than 10 mm. Any radiological diagnosis should 
take this evolving anatomy into account. 

Brain malformations, mostly commissural agenesis, 
form about one-third of the diagnoses. The group of the 
ventriculomegalies (above 10 mm) forms the most com- 
mon indication (40%); their prognosis is worse if MRI 
uncovers associated abnormalities (e.g. cortex malforma- 
tions, loss of the tissular layered pattern, necrosis, haem- 
orrhage) often not seen at US. Foetal hydrocephalus may 
develop without the skull being enlarged. 

Better Prognostic Assessment of Neonatal Disease with 
MRI 

The expression of CNS disease in the neonate is poor: 
failure to thrive, convulsions. US is the first, often the 
sole investigation of the neonatal brain. Operator-depen- 
dent, it should be performed according to a strict proto- 
col so that the images can be read by any concerned 
physician; this protocol does not exclude focussing on 
specific abnormalities also, as they are discovered during 
the study. 

The typical features of anoxic-ischaemic en- 
cephalopathies (AIE) are well correlated with the gesta- 
tional age. In the premature infant, MRI shows: 

- various degrees of subependymal haemorrhages (SEH) 
with germinal matrix clots, ventricular clots, and par- 
aventricular haemorrhagic venous infarctions, and 

- periventricular leucomalacia (PVL) with diffuse 
periventricular abnormalities. 



In the term baby, MRI shows necrosis of the central 
nuclei (short Tl, short or long T2) and cortex (loss of 
contrast, abnormal cortical T1/T2 signal, especially in the 
depth of the sulci), global brain swelling and venous 
thrombosis. The T1/T2 shortening should not be con- 
fused with normal early myelination. A diffuse, thin sub- 
dural haematoma over the tentorium cerebelli due to de- 
livery is common even in normal neonates, and a few 
punctiform parenchymal haemorrhages along the ventric- 
ular wall and in the parenchyma may be observed. 

CT can be used in AIE as it has fewer constraints than 
MRI. However, the prognosis is best approached with 
MRI: severity and extent of the lesions, and metabolic ap- 
proach with proton spectroscopy (abnormal lactate peak). 
On CT, the relatively low density of the parenchyma as 
compared with the blood in the dural sinuses should not 
be misread as venous thrombosis. 

Other neonatal disorders include malformations, in- 
fections, perinatal trauma and breathing failure. A nearly 
normal-looking brain in a severely ill neonate points to a 
metabolic disease. 

MRI Is the Primary Tool for Assessing Increased 
Intracranial Pressure 

Increased intracranial pressure (ICP) is expressed in the 
young infant by enlargement of the head with bulging 
fontanel, sometimes with a “sunset gaze” (Parinaud’s 
syndrome), and in older children by headaches, lethargy 
and vomiting. The most common causes of increased ICP 
in children are hydrocephalus or lesions associated with 
hydrocephalus, and less commonly, mass lesions without 
hydrocephalus and diverse pathologies such as venous 
thrombosis. 

Hydrocephalus Should Be Evaluated with MRI 

The skull contains CSF, blood and brain tissue. 
Hydrocephalus is due to increased resistance to circula- 
tion or decreased resorption of CSF. The CSF compart- 
ment expands actively against the blood (acutely) and or 
the cellular compartments (subacutely or chronically). 
The CSF and extracellular spaces are in continuity, so the 
latter tends to expand also in case of hydrocephalus. The 
periventricular hyperhydration observed in hydro- 
cephalus is a superadded brain oedema rather than a use- 
ful resorption process. In the yoimg infant, hydrocephalus 
can be detected with US but, like in older patients, it 
should be assessed by MRI to: 

- Ascertain the hydrocephalus: increased head circum- 
ference, enlarged ventricles with rounded temporal 
horns and compressed hippocampi (never observed in 
atrophy). 

- Locate the obstacle: uni-, bi-, tri- or quadriventricular 
hydrocephalus; cisternal block; peripheral block. 
Triventricular hydrocephalus is not necessarily an 
aqueductal stenosis, which should be documented. 
When a ventricular block is downstream of the anteri- 




114 



C. Raybaud 



or third ventricle, ventriculocisternostomy may be per- 
formed, avoiding insertion of a shunting device. 
Documenting the freedom of the extracerebral CSF 
pathways is possible using flow-sensitive sequences 
and high definition T2-weighted imaging. 

- Look for complications', circulatory arrest in acute 
block (loss of gray-white matter contrast, usually with 
small, rounded ventricles); herniations; periventricular 
oedema; loss of brain substance (only in the first 
months of life has the brain the capacity to recover its 
full thickness); demyelination, etc. 

- Identify the cause (together with the clinical context), 
and prepare for treatment. Overall, 80% of paediatric 
brain tumours develop in or around the ventricles. 
Brain malformations, cavitations and cysts within and 
around the brain may accumulate fluid. Trauma, infec- 
tions and haemorrhages may reduce the resorption ca- 
pabilities. 

Some infants, especially former premature infants, 
present benign idiopathic external hydrocephalus, an ac- 
cumulation of fluid over the anterior frontotemporal con- 
vexities, with mild anterior ventricular enlargement, and 
macrocephaly. As a rule, it disappears spontaneously af- 
ter 18 months. The assumed pathogenesis is immaturity 
of the arachnoid granulations. Similar features may ex- 
press an increased venous pressure in infants. 

Mass Effects: Tumours and Other Lesions 

Any mass effect may induce features of increased ICP, 
even without producing hydrocephalus. The most com- 
mon causes in children are pericerebral haematomas 
(mainly subdural), hemispheric tumours, intracerebral 
bleeding, expanding extracerebral arachnoid cysts, and 
septic abscesses and empyemas. In cerebral throm- 
bophlebitis, brain oedema may develop as the sole symp- 
tom (so-called pseudotumour cerebri). 

Peculiar aspects of brain tumours in children are their 
frequency (second only to leukaemias), diversity, fre- 
quent dissemination along the CSF spaces (spine imag- 
ing is mandatory to complement brain imaging) and pos- 
itive correlation between age and topography and histol- 
ogy (e.g. juvenile pilocytic astrocytoma (JPA), medul- 
loblastomas, choroid plexus papillomas, fibrillary astro- 
cytoma of the pons). Further information on this topic 
should be looked for in specialized textbooks. 

Some tumours are special as they are cortical, devel- 
opmental and highly epileptogenic. In children, the most 
common is ganglioglioma, the most specific is infantile 
dysplastic neurocytoma, and the most typical is dysem- 
bryoplastic neuroepithelial tumour (DNET). 

Craniocerebral Trauma May Produce Specific Lesions 
in Children 

In grown children, trauma is not different from what it is 
in adults. In young infants it is different because of the 
different physical properties of the infantile skull and 



brain and of the different circumstances. The elasticity of 
the squamous vault explains the special appearance of the 
“table-tennis ball fracture”. The malleability of the cal- 
varium, without rigid sutures, favours the development of 
shearing lesions, within the meninges (acute subdural are 
more common than acute epidural hematomas) and with- 
in the brain. The delivery itself is a specific process with 
specific lesions. 

Above all, young children may be victims of nonacci- 
dental trauma. The most common mechanism is shaking 
that causes brain lesions aggravated by the lack of tonus 
of the neck muscles. The main clinical features are de- 
creased consciousness and convulsions; fundoscopic ex- 
amination typically discloses retinal haemorrhages (shak- 
ing-related tractions on the optic ner\^es). Intracranial ex- 
amination may demonstrate multiple subdural 
haematomas of different signals (MRI) or intensities 
(CT), explained either by different dilutions with CSF or 
by different times of occurrence. A thin lining of acute 
subdural bleed along the falx is especially suggestive. 
These bleeds are explained by the rupture of bridging 
veins; they are accompanied by areas of ischaemia (areas 
of low signal with loss of the gray- white matter contrast, 
commonly bilateral in the frontal or temporo-occipital ar- 
eas, and oedema). Further investigation may disclose 
multiple fractures (skull, ribs, long bones) at various 
stages of consolidation. The haematomas may be drained, 
but the bilateral cerebral lesions are usually devastating 
with subsequent encephalomalacia and cerebral atrophy. 

Acute Neurological Deficits 

Intracerebral Haemorrhage Needs an Emergency 
Diagnosis 

Intracerebral haemorrhages in children are absolute 
emergencies. A child may be playing at school, complain 
of a sudden headache, go into coma, and die in a few 
hours. There is absolutely no spontaneous brain haemor- 
rhage in children and, except in rare cases of coagulation 
disorders, causes to be looked for are AVMs (in children, 
80% are revealed by bleeding) and cavernomas (usually 
less severe). The diagnosis should be made as quickly as 
possible, as surgery is the only way to alleviate the in- 
tracranial pressure; it is then better to remove the causal 
AVM together with the blood collection. The nidus of the 
AVM may be well seen on conventional imaging, espe- 
cially MW. The vasculature of the AVM may be well de- 
picted by MR angiography. Conventional intra-arterial 
angiography is needed when endovascular treatment is 
considered. 

Arterial Ischaemia of the Brain Is Not Rare in Children 

Brain arterial ichaemia is different in children and adults, 
because the vascular pathologies are different, the meta- 
bolic needs and cerebral blood flow are higher in chil- 




Central Nervous System Diseases in Children 



115 



dren, and the haemodynamic protection (cerebral au- 
toregulation and collateral anastomoses) is usually higher 
in children. In cases of profound and prolonged drop of 
the central perfusion pressure, ischaemic lesions affect 
primarily the structures with high metabolism (central 
nuclei, cortex), with a watershed distribution. 

Arterial occlusions in children occur mainly at the ter- 
minal portion of the carotid siphons and the proximal 
segments of the cerebral arteries: clots stop there because 
they cannot go beyond the bifurcations. This segment is 
the one involved in virus-related vasculitis. It is directly 
affected by the inflammatory process of septic meningi- 
tis. As a common result, the lenticulostriate perforators 
become occluded at their origin, with necrosis of the 
basal ganglia and deep paraventricular white matter, 
while the widely efficient corticopial anastomoses pro- 
tect the cortical territories downstream of the occlusion. 
So, typical cerebral ischaemia in children affects the 
striatum only, sparing the cortex; functional recovery is 
usually good and recurrences are uncommon. However, 
when the occlusive process is extensive, several arteries 
(e.g. anterior choroidal, anterior cerebral) may be oc- 
cluded, affecting the internal capsule also and compro- 
mising the sources of the collateral flow. 

The spectrum of aetiologies is extremely large in chil- 
dren: embolic occlusion, usually from heart disease; sep- 
tic infections adjacent to the arterial tree (cervical ade- 
noiditis, tonsillitis, septic meningitis); virus-related arte- 
rial vasculitis (chickenpox, herpes); trauma (cervical, 
pharyngeal); haemopathies (sickle cell disease); and 
metabolic diseases (homocystinuria). 

One arterial dysplasia, moyamoya, is quite specific 
and is characterized by stenosis of the carotid siphons and 
of the proximal segments of the middle and anterior cere- 
bral arteries, sparing the posterior circulation. As the 
stenosis is slowly progressive, collateral networks devel- 
op and may compensate the occlusion temporarily. They 
use the small pial arteries, the deep anastomoses between 
the lenticulostriate and the cortical perforators (aspect of 
“puff of smoke”, moyamoya in Japanese), and the dural- 
pial anastomoses. With progression of the disease, in- 
farctions occur repeatedly. On imaging, multiple lesions 
of different ages and global atrophy may be observed. 
Medical and surgical treatments are proposed. 
Moyamoya disease is an idiopathic, maybe genetic disor- 
der. Moyamoya syndromes present with similar images 
and may be observed in different clinical contexts such as 
sickle cell disease, neurofibromatosis type I, and as a 
complication of radiotherapy to the sellar region. 

CNS Infections 

Septic Infections May Present Severe Complications 

Septic infections of the CNS are not essentially different 
in children and adults. However, the immature brain is 
particularly vulnerable (massive abscesses with tissue de- 



struction) and infants present special complications such 
as subdural “effusions” that become secondarily infected 
and form subdural empyemas (meningeal abscesses). In 
neonates, specific vaginal germs are involved {Proteus 
and Citrobacter); these may produce giant abscesses with 
massive destruction of brain tissue. In all children, ven- 
triculitis, meningeal fibrosis and subsequent hydro- 
cephalus are common. 

Viral Infections Can Be Devastating 

Viral lymphocytic meningitides are common in children, 
and usually benign. Encephalitides are clinically impres- 
sive but usually benign, with sometimes ill-defined areas 
of long T1/T2 affecting both the gray matter and white 
matter. They may be severe when they are due to a her- 
pesvirus, or when they develop in immunodeficient chil- 
dren. Two types of herpes encephalitis occur in children: 

- Herpes type I encephalitis, not different from what it 
is in adults, concerns older children, presumably due 
to infestation from the trigeminal nerve. The necroti- 
cohaemorrhagic destructions affect mostly the mesial 
temporal lobes and adjacent fronto-orbital cortex (pos- 
sibly having special tropism for the limbic structures). 
Untreated or treated late, the lesions are devastating, 
particularly when vasculitis develops in addition. 

- Herpes type II concerns the neonate contaminated dur- 
ing the birth process by a mother with genital herpes. 
The viremic diffusion results in a massive destruction 
of the parenchyma. It can be avoided by systematic use 
of caesarean section in affected mothers. 

Worldwide, the most deadly encephalitides are due to 

arboviruses, such as the Japanese B encephalitis virus. In 
Europe, mumps, measles, rubella, and infections with 
Epstein-Barr virus and coxsakie viruses are common. 
Varicella-zoster (chickenpox) affects mostly the cerebel- 
lum, but also the arteries. Subacute sclerosing panen- 
cephalitides rarely may develop after measles or rubella. 

Acute Disseminated Encephalomyelitis Is a Common 
Immune-related Disorder 

Acute disseminated encephalomyelitis (ADEM) is a 
postinfectious, acute, immuno-allergic demyelination 
that affects mostly children and young adults. It devel- 
ops within a few days after a febrile episode, typically 
viral but possibly bacterial, or after an immunisation. It 
is expressed on imaging by areas of oedematous de- 
myelination, sometimes extensive, affecting both gray 
matter and white matter, in the brain and spinal cord. The 
lesions are not symmetrical, and may or may not en- 
hance with contrast agents. Histologically, only the 
myelin sheath is affected, not the oligodendrocyte, and 
recovery usually occurs in a few weeks or months. 
Relapsing forms exist, causing borderline to chronic de- 
myelination such as multiple sclerosis (MS). Schilder’s 
disease is controversial and has been classified both as a 
form of MS and a form of ADEM. The prognosis de- 




116 



C. Raybaud 



pends on the causal virus: smallpox ADEM used to re- 
sult in significant mortality; measles ADEM leaves neu- 
rologic sequelae in about 15% of cases. Idiopathic 
ADEMs are commonly benign. Acute disseminated 
haemorrhagic myelitis (AHEM) is an especially severe 
form of ADEM. Transverse myelitis is likely to be a pre- 
dominantly spinal form of ADEM. 

Degenerative, Progressive Encephalopathies Are Fairly 
Common 

There is no room to fully describe the degenerative en- 
cephalopathies. These are metabolic disorders, classified 
according to the clinical picture correlated with the en- 
zymatic defect (e.g. mitochondriopathies, peroxisomal or 
lysosomal defects, disorders of intermediate metabolism, 
aminoacidopathies). Each is rare, but the causal multi- 
plicity is such that, as a group, they are common and 
probably underdiagnosed. They affect predominantly the 
white matter (leucodystrophies) or the gray matter (po- 
liodystrophies), or both. Their clinical course is typically 
progressive. A familial history of similar disorders, or of 
consanguinity, is common. Some have typical features on 
MR images, with a specific organisation of the anomalies 
(adrenoleucodystrophies, metachromatic leucodystro- 
phies, Alexander’s disease, Canavan’s disease, Wilson 
disease’s, etc.). Others present with different patterns in 
different patients (most mitochondriopathies). The anom- 
alies (posterior or anterior; central or subcortical; affect- 
ing or not the corpus callosum, basal ganglia, brain stem 
or cerebellum; with or without craniomegaly, cysts, cal- 
cification, enhancement; mode of progression, etc.) typi- 
cally are symmetrical, while the inflammatory lesions 
typically are not. When the images are not specific, MR 
spectroscopy may be useful, but the diagnosis fundamen- 
tally rests upon the clinical picture, familial history and 
biological data. 

Malformations 

Cord and Spine 

The processes leading to formation of the spine and cord 
start with the development of the midline mesodermal 
structure that induces the transformation of the midline 
dorsal ectoderm into a neural ectoderm. The vertebral 
centrum is organised around the notochord independent- 
ly from the cord, and the neural arches develop around 
the cord independently from the vertebral centrum. The 
malformations may be classified into disorders of the no- 
tochord, cord (with or without the neural arches) and ver- 
tebral centrum, and disorders of segmentation. 

1. Notochord anomalies. The persisting neurenteric 
canal or cysts are cysts anterior to the cord in the 
spinal canal, the spine itself, the mesenterium or the 
mediastinum (bronchogenic cysts). Exceptional, they 
represent the abnormal persistence, typically in the 



cervicodorsal or dorsolumbar segments of the spine, of 
the normally transient neurenteric canal. Diastemato- 
myelia and diplomyelia are presumably related to a du- 
plication of the notochord with duplication of the cord 
and attempted duplication of the spine. 

2. Cord anomalies. The most common cord anomaly 
worldwide is myelomeningocele, in which the neural 
tube fails to close and remains exposed on the back 
of the child, with an open spinal canal. As a rule, it is 
associated with brain stem and cerebellum displaced 
into the cervical canal, a small posterior fossa, and 
hydrocephalus, forming the Cltiari II deformity. 
Dermal sinuses and cysts develop when the skin re- 
mains attached to the cord, forming a fistula behind 
and below the cord that tends to become infected. A 
lipomeningocele is a dysplastic lipoma developing 
through a spinal hiatus between the cord and the sub- 
cutaneous fat. Sacral agenesis is a missing distal seg- 
ment of the spine, together with a lack of the corre- 
sponding segment of the cord. Chiari I “malforma- 
tion" and hydrosyringomyelia are likely to be related 
to disturbances of CSF dynamics. All these diseases 
associate anomalies of the neural arches with anom- 
alies of the cord. 

3. Vertebral center anomalies. As a rule, vertebral center 
anomalies are not associated with cord anomalies. 
Examples of vertebral center anomalies include com- 
plete or partial agenesis and butterfly vertebra with 
persisting notochordal remnants. 

4. Segmentation disorders (hemivertebrae) are probably 
mesodermal (somitic) and are not associated with cord 
anomalies. 

Gross Brain Malformations 

The most common gross brain malformation worldwide 
is the Chiari II malformation that associates a closure de- 
fect of the neural tube with (probably subsequent) defor- 
mity of the hindbrain in a small posterior fossa, and oth- 
er dysplasias of the neural tube. A failure of the forebrain 
vesicles to differentiate properly results in various de- 
grees of interhemispheric fusion with missing septum 
pellucidum, the holoprosencephalies, sometimes with fa- 
cial anomalies. Several gene defects may be involved. 

Septo-optic dysplasia is characterized by the absence 
of septum pellucidum, dysplasia of the anterior optic 
pathways, and a pituitary deficit. 

Commissural agenesis (so-called callosal agenesis) is 
when one or several commissures (anterior, hippocampal, 
callosal) fail to develop, totally or partially, between the 
hemispheres, usually together with other white matter 
tracts. It may be associated with cystic or lipomatous dys- 
plasia of the inter-hemispheric meninges. 

In the hindbrain, developmental anomalies of the roof 
of the fourth ventricle result in cystic malformations of 
the posterior fossa, with an elevated tentorium, with or 
without vermian agenesis. These conditions form, as a 
group, the spectrum of Dandy-Walker malformations. 




Central Nervous System Diseases in Children 



117 



Malformations of Cortical Development (Brain and 
Cerebellum) 

The development of the mantle and cortex proceeds in 
subsequent steps, and cortical malformations corre- 
spond to the failure of any of these. The first step is pro- 
liferation; its failure results in micrencephaly with sim- 
plified gyral pattern. The second step is differentiation 
into neurons and glia; its failure results in focal cortical 
dysplasias (FCD), microdysgenesis or hemimegalen- 
cephaly, all characterized by poor cellular differentia- 
tion, migration and a poor organisation. Tuberous scle- 
rosis is a syndromic, genetic form of cortical dysplasia. 
If normal neurons fail to migrate properly, they form 
heterotopias, either nodular heterotopias (periventricu- 
lar or subcortical) or laminar heterotopias (also called 
“double-cortex” and band heterotopias). Depending on 
the gene defect, they can be mostly anterior (chromo- 
some X) or posterior (chromosome 17). Agyrias-pachy- 
gyrias are more complete forms of double-cortex, with 
an absent or simplified gyral pattern. If the migration is 
adequate but the cortical organisation is not, polymicr- 
ogyria develops, uni- or bilateral, with an aberrant sul- 
cal pattern. The rare schizencephaly is a trans-mantle 
cleft lined with polymicrogyric cortex, either uni- or bi- 
lateral. 

Most of these disorders are epiletogenic, with or with- 
out neurologic deficits. For some, developmental tumours 
may be classified as cortical dysplasias. 

Neuroectodermal Syndromes of Brain, Skin 
and Other Organs 

Neurofibromatosis type 7, the most common genetic dis- 
order, is characterised by multiple cutaneous lesions, es- 
pecially cafe-au-lait spots. CNS anomalies, when they 
occur, develop in the young child. The most spectacular 
is juvenile pilocytic astrocytoma of the optic pathways 
and of the anterior third ventricle, which may be severe 
but may also be dormant and even regress spontaneous- 
ly. The most typical is the presence of multiple areas of 
high T2/FLAIR signal intensity distributed in the globi 
pallidi, posterior thalami, brain stem and cerebellar white 
matter. They exert no or little mass effect, and do not en- 
hance. They disappear at adulthood. Other masses may 
develop - and regress - elsewhere, especially in the brain 
stem. Malignant degeneration may occur. Arterial dys- 
plasia with giant cervical aneurysms or moyamoya may 
be present. In the peripheral nervous system (PNS), neu- 
rofibromas may develop, often plexiform, with potential 
transformation into neurofibrosarcomas. Agenesis of the 
greater wing of the sphenoid, vertebral scalloping and 
dural ectasias may be observed. 

Neurofibromatosis type II is much less common; it 
may develop during the second and third decades of life 
or about the fifth. The disease is characterised by the de- 
velopment of multiple schwannomas (especially acoustic. 



but also trigeminal, spinal or others), multiple menin- 
giomas and cervical cord ependymoma. The unrelenting 
development of these tumours makes the disease devas- 
tating. 

Tuberous sclerosis may affect the skin, heart, kidney, 
pancreas, lung and brain. The cerebral lesions usually 
include multiple cortical tubers, subependymal nodules 
and trans-mantle abnormalities. All are characterised by 
the presence of so-called giant astrocytes, which are ac- 
tually undifferentiated neuronoglial cells. The disease is 
genetic and highly epileptogenic. Subcortical nodules in 
the vicinity of the interventricular foramen of Monro 
may develop into slow-growing tumours and need re- 
moval. 

In Stiirge-Weber disease, there are pial angiomas of the 
posterior part of the hemisphere, metamerically associat- 
ed with retinal angioma, enlarged choroid plexus, facial 
port-wine angioma in the territory of the ophthalmic 
branch of the trigeminal nerve, and abnormal draining 
veins of the affected hemisphere. Pial calcifications de- 
velop. The disease is usually epileptogenic and causes 
progressive atrophy of the hemisphere. 

Childhood Epilepsy Develops According to 
Age-specific Patterns and Syndromes 

Epilepsy is a chronic disease, and it must be differentiat- 
ed from the acute, symptomatic seizure. In children, its 
clinical expression is age-related; it usually presents as 
specific syndromes with specific treatments and specific 
prognoses. Epilepsy is grossly classified into an idio- 
pathic benign form (familial, often transient) with normal 
brain, and a symptomatic form when the brain is abnor- 
mal. Any chronic brain alteration, either acquired (e.g. af- 
ter anoxic-ischaemic insults, infections, traumatic scar- 
ring) or inborn (e.g. malformations, developmental disor- 
ders), may cause epilepsy. 

Imaging is necessary to illustrate the potential cause 
of the disease, as well as its effects on the brain. It may 
also demonstrate surgically accessible lesions such as 
developmental tumours or focal cortical dysplasia (FCD). 
When no abnormality is found at imaging, the epilepsy 
is said to be cryptogenic. 

Chronic Encephalopathies 

Mental retardation, associated or not with cerebral pal- 
sy or epilepsy, is probably the most common indication 
for brain imaging in children. The clinical context and 
the personal and familial histories are diverse. As for 
epilepsy, any lesion usually affecting the brain diffuse- 
ly, either acquired or developmental, may be observed. 
Some are peculiar, such as subtle dysmorphism of the 
corpus callosum or cerebellar cortical dysplasias. 
Others are non-specific, such as diffuse atrophy or in- 
complete myelination. 




IDKD 2004 



Orbit and Visual Pathways 

M.E Mafee*, D.M. Yousem^ 

^ Department of Radiology, University of Illinois, Chicago, IL, USA 

^ Department of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins 
Medical Institution, Baltimore, MD, USA 



Introduction 

The various compartments of the orbit lend themselves to 
a geographical analysis of lesions involving the orbit. 
Thus one often finds classifications of orbital diseases 
describing ocular abnormalities involving the globe vs. 
intraconal non-ocular abnormalities involving the soft tis- 
sues within the muscular cone, conal abnormalities in- 
volving the extraocular muscles, and extraconal abnor- 
malities involving those lesions outside the muscular 
cone. In addition there are specific diseases that affect the 
orbital “appendages”, which include the lacrimal glands, 
lacrimal sac, and conjunctivae. 

Within each of these categories one might use the 
mnemonic of VITAMIN C AND D to evaluate lesions 
classified into vascular, inflammatory, traumatic, ac- 
quired, metabolic, idiopathic, neoplastic, congenital, and 
drug-related entities. 

Anatomic Considerations 

The orbital recesses contain the globes, cranial nerves II, 
III, IV, V and VI, muscles, blood vessels, connective tis- 
sue, and most of the lacrimal apparatus. The bony orbit is 
bordered by the periosteum (the periorbita or orbital fas- 
cia), which is loosely adherent to the surrounding bones 
except at the trochlear fossa, lacrimal crests and margins 
of the fissures and canals where it is more tightly bound. 
Anteriorly, at the margins of the orbit, the periorbita is 
continuous with the orbital septum, a membranous sheet 
forming the fibrous layer of the eyelids. Tenon’s capsule 
(fascia bulbi) is a fibroelastic membrane that envelops 
the eyeball from the optic nerve to the level of the ciliary 
muscle. The inner surface of Tenon’s capsule is separated 
from the outer surface of the sclera by a potential space, 
the episcleral or Tenon’s space. The intraorbital structures 
are embedded in a fatty reticulum. This is divided into: 
(1) peripheral orbital fat outside the muscle cone, and its 
intermuscular membranes, and (2) the central orbital fat, 
which is within the muscle cone. The fibroelastic tissue 
comprising the reticulum divides the fat into lobes and 



lobules. The four recti and two oblique muscles control 
eye movement. The recti muscles arise from the annulus 
of Zinn, a funnel-shaped tendinous ring, which encloses 
the optic foramen and medial end of the superior orbital 
fissure. 



Ocular Imaging 

The eye consists of three primary layers: (1) the sclera, or 
outer layer; (2) the uvea, or middle layer; and (3) the reti- 
na, or inner layer which is the neural, sensory stratum of 
the eye. The retina has two layers: the inner layer is the 
sensory retina and the outer layer is the retinal pigment 
epithelium (RPE), a single lamina of cells whose nuclei 
are adjacent to the basal lamina (Bruch’s membrane) of 
the choroid. The vitreous body occupies the space be- 
tween the lens and retina and represents about two-thirds 
of the volume of the eye. There are basically three poten- 
tial spaces that can accumulate fluid, resulting in detach- 
ment of various coats of the globe: 

1. Posterior hyaloid space, the potential space between 
the base (posterior hyaloid membrane) of hyaloid and 
sensory retina. Separation of posterior hyaloid mem- 
brane from the sensory retina is referred to as posteri- 
or hyaloid detachment; 

2. Subretinal space, the potential space between the sen- 
sory retina and RPE. Separation of sensory retina from 
RPE is referred to as retinal detachment; 

3. Suprachoroidal space, the potential space between the 
choroid and the sclera. The RPE and Bruch’s mem- 
brane are tightly adherent to the choroid and become 
separated when both layers are torn; however, the 
choroid is loosely attached to the sclera and can be 
separated resulting in choroidal detachment. 

Blood within the anterior chamber of the globe causes 
a density difference between the affected globe and the 
unaffected globe, which is visible on computed tomogra- 
phy. This has been termed anterior hyphema and is read- 
ily apparent on ophthalmologic evaluation. It is rare to 
see isolated blood in the posterior chamber since this is a 
relatively small space intimately associated with the cil- 




Orbit and Visual Pathways 



119 



iary apparatus. After trauma, one may see rupture of ei- 
ther the anterior chamber (where there is flattening of the 
globe anterior to the lens) or of the vitreous humor. The 
latter, more commonly diagnosed by radiologists, appears 
as a globe that is subtly or grossly abnormal in shape 
rather than spherical. Hemorrhage may be identified by 
the difference in density in the two globes within the vit- 
reous humor. 

Choroidal or retinal detachments may be associated 
with globe trauma or rupture and with some neoplasms. 
Most retinal detachments have an elliptical V-shaped ap- 
pearance in which the most posterior margin of the de- 
tachment is intimately associated with the optic nerve in- 
sertion and extends anteriorly to the ora serrata. Choroidal 
detachments extend farther anteriorly to the ciliary appa- 




ratus and may not be restricted by the optic nerve insertion. 
They are anchored by the vortex veins or ciliary arteries. 

Leukocoria refers to a white reflex when a light is shined 
in the patient’s eyes. This is a finding that clinically elicits a 
wide differential diagnosis, however on imaging one should 
consider disease entities such as retinoblastoma (Fig. 1), 
persistent hyperplastic primary vitreous (PHPV), and 
Coats’ disease in children. PHPV is due to persistence of 
primary vitreous along Cloquet’s canal; one can see a fine 
thread of this residual hyaloid vascular system extending 
from the (small, anteriorly located) lens to the optic nerve. 
The globe often is small and noncalcified (distinguishing it 
from retinoblastoma) and may have variable signal intensi- 
ty on magnetic resonance imaging (MRI). Coats’ disease is 
due to retinal vascular malformation with associated exuda- 




Fig. la-c. Retinoblastoma with involvement of optic nerve, a Axial 
unenhanced T1 -weighted MR image, b Axial T2-weighted MR im- 
age. c Enhanced fat-suppressed T1 -weighted MR image 






120 



M.F. Mafee, D.M. Yousem 



tive retinal detachment. Toxocara canis infection may also 
cause leukocoria in a child. Once again, retinal detachment, 
increased ocular density, and absence of calcification char- 
acterize this entity. Retinopathy of prematurity may lead to 
noncalcified microphthalmic globes and leukocoria. High 
oxygen saturation exposure because of bronchopulmonary 
disease in a premature infant is likely the etiology. 

Colobomas are congenital lesions of the globe in which 
there is an outpouching, usually at the optic nerve inser- 
tion, where the optic fissure vesicle closes. Colobomas 
may appear as two globe-like structures in the orbit; the 
classic clinical finding is “morning glory syndrome” in 
which there is a “black eye” reflex. The coloboma may 
lead to focal expansion of the optic nerve head insertion 
itself It is important to look for central nervous system 
midline anomalies in patients with coloboma. 

By the same token, cyclopia may be associated with 
holoprosencephaly intracranially. Even when there are 
two globes associated with holoprosencephaly, one 
should survey for the presence of optic nerve hypoplasia, 
which is found in all forms of the spectrum of holopros- 
encephaly, including septo-optic dysplasia. In the latter 
entity, the septum pellucidum is absent and there is a high 
rate of schizencephaly. 

In a patient infected with human immunodeficiency 
virus (HIV), a common cause of ocular infection is cy- 
tomegalovirus (CMV) retinitis. This may lead to retinal 
detachment as well as to choroidal abnormalities and ab- 
normalities of the ciliary body. 

The most common primary ocular malignancy in 
adults is melanoma. This usually affects the choroid of 
the globe. Spread of uveal melanoma within the globe or 
along the optic nerve sheath into the subarachnoid space 
must be considered. Melanoma may be hyperdense on 
noncontrast computed tomography (CT) and have unusu- 
al MRI signal intensity characteristics (bright on T1 and 
dark on T2-weighted images) because of the melanin 
content. It will usually enhance. 

Metastatic disease to the globes should also be con- 
sidered in adult patients with ocular masses. Breast, lung 
and kidney primary tumors should be suspected. Often 
they are clinically silent and found only at the time of eye 
donation. The tumor is deposited in the choroid or retina 
and is bilateral in one-third of cases. 



Orbital Appendages 

Non-neoplastic abnormalities of the lacrimal glands are 
usually divided into those related to granulomatous disease, 
lymphoid lesions, and germ-line lesions. Granulomatous 
diseases include infectious etiologies such as tuberculosis 
and fiingal disease as well as sarcoidosis. Additionally, 
pseudotumor of the orbit may affect the lacrimal gland as 
an idiopathic granulomatous inflammatory condition. 

One should also consider epidermoid lesions as well as 
dermoids. Both result from the inclusion of ectodermal 
elements during closure of the neural tube. Both have a 



fibrous capsule of varying degrees of thickness. The epi- 
dermoid cyst has a lining of keratinizing, stratified ep- 
ithelium. The dermoid cyst contains one or more dermal 
adnexal structures such as sebaceous glands and hair fol- 
licles. Dermoid cysts are found laterally in the orbit and 
85% present with bony changes, usually remodeling. 
Low density (46%), calcification (14%), and purely cys- 
tic nature (80%) characterize these lesions. 

In general, epithelial tumors represent 50% of masses 
involving the lacrimal gland. The remaining 50% of 
lacrimal gland masses are the lymphoid-inflammatory 
type. The excellent prognosis for benign mixed tumor, pro- 
vided it is completely excised at first surgery, necessitates 
that these lesions should not undergo incisional biopsy, but 
require en bloc excision along with adjacent tissues. 

Less commonly, neoplasms associated with adenocar- 
cinomas and adenoid cystic carcinoma can arise in the 
lacrimal glands. Lymphoma, post-transplant lymphopro- 
liferative disorders, and Sjogren’s disease may affect the 
lacrimal gland. Most orbital lymphomas are composed of 
monoclonal B cells. Roughly 10% of non-Hodgkin’s lym- 
phomas present in the head and neck region. Lymphoid 
tumors account for 10%-15% of orbital masses. 

The lacrimal sac and lacrimal duct are potential areas 
of congenital pathology as well. Congenital lesions in- 
clude dacryocystoceles in which there is marked bulbous 
enlargement of the descending portion of the lacrimal 
duct, most commonly from maldevelopment of the valves 
that produce the appropriate downward flow of tears into 
the inferior meatus of the nasal cavity. These may present 
as medial orbital lesions or as sinonasal lesions. 
Obstruction of the ductal system may occur due to in- 
flammatory condition of the paranasal sinuses or a direct 
infection of the duct itself In these cases the patient may 
present with epiphora (excessive tearing). A number of ar- 
ticles have been written concerning the benefit of balloon 
angioplasty and stenting of the ducts to improve the flow 
of tears. This may also be a complication of paranasal si- 
nus or orbital surgery and of radiation therapy. 

Skin cancers such as squamous cell carcinoma and 
basal cell carcinoma may affect the lacrimal sac. 
Traditionally, transitional cell carcinoma may affect the 
lacrimal sac as the lining cells of the ductal system lead- 
ing to the sac or leading from the sac. The lacrimal sac 
may also be affected by lymphoma. Inflammatory condi- 
tions of the lacrimal sac include pseudotumor of the or- 
bit and dacryocystitis secondary to any number of the in- 
fectious lesions that affect the conjunctivae or from ret- 
rograde spread from sinus infection. The agger nasi cell 
of the anterior ethmoid complex has a particular propen- 
sity for eliciting epiphora as the sac and proximal duct are 
exposed in this location of sinus infection. 

Intraconal Lesions 

The most common benign intraconal mass is the heman- 
gioma. This may in fact be a venous vascular malforma- 




Orbit and Visual Pathways 



121 



tion (VVF), and it has been reclassified recently in most 
head and neck treatises. If one finds phleboliths within a 
mass in the intraconal compartment, one should consider 
a venous vascular malformation vs. venous varix. These 
enhance avidly and are usually quite bright on a T2- 
weighted scan. The differential diagnosis with VVF in the 
intraconal compartment includes a schwannoma of 
trigeminal or oculomotor nerve origin or a metastasis. 

An orbital varix may be diagnosed through various 
manipulations that can be performed while the patient is 
in the scanner. In many cases, a simple Valsalva’s ma- 
neuver while performing the CT scan through the orbit 
will show the marked enlargement of the varix as the 
pressure changes lead to its dilatation from a resting state. 
Alternatively, one may place the patient in a head-back 
supine position, which may also increase the intraconal 
pressure sufficiently to change the size of the varix, 
which makes the diagnosis. Benign hemangiomas may 
also enlarge with such a maneuver, however, but the var- 
ix usually takes the form of the superior ophthalmic vein 
with its characteristic course. 

Optic nerve sheath meningiomas and optic nerve le- 
sions are also found in the intraconal compartment. 
Classically the optic nerve sheath meningioma appears 
as enhancement of the lining of the optic nerve without 
direct optic nerve enlargement. Sometimes, however, 
when the lesion is quite large it is difficult to distinguish 
from an intrinsic optic nerve lesion. Intrinsic optic nerve 
lesions include the optic nerve glioma, which is often as- 
sociated with neurofibromatosis. In this instance the op- 
tic nerve is diffusely enlarged and may show extension 
along the entire optic pathway even into the occipital 
lobes. Optic nerve glioma in children is a benign, well- 
differentiated, and slow growing tumor. Bilateral optic 
nerve gliomas are characteristic of type 1 neurofibro- 
matosis (NFl). The natural history of childhood optic 
glioma does not involve malignant transformation or 
systemic metastasis. Local invasion into the extraocular 
muscles (EOMs) rarely occurs. Malignant optic glioma 
is primarily seen in adults. It is a rare, fatal disease 
(glioblastoma multiforme) that usually extends from in- 
tracranial glioma. CT shows an enlarged fusiform and 
kinked optic nerves, along with marked to moderate en- 
hancement. 

These two neoplasms of the optic nerve and sheath 
should be distinguished from inflammatory conditions 
such as pseudotumor and demyelinating conditions such 
as optic neuritis. The latter is seen as abnormal signal in- 
tensity within the orbit on coronal, fat-saturated, T2- 
weighted scans or as enhancement of the optic nerve on 
fat-saturated post-gadolinium-enhanced scans. One can 
also see infectious inflammatory lesions affecting the op- 
tic nerve and sheath, particularly herpes infection with 
herpes zoster ophthalmicus, sarcoidosis, tuberculosis, and 
toxoplasmosis. Finally, neoplastic spread along the sub- 
arachnoid space of the optic nerve sheath should be con- 
sidered in any patient with ocular melanoma, retinoblas- 
toma, leukemia, lymphoma or metastases to the orbit. 



Ischemic optic neuropathy (ION) is an entity seen in 
the elderly who present with painless visual loss. One 
may see high signal intensity in the optic nerve on T2- 
weighted images in the acute phase, followed by optic at- 
rophy in the chronic phase. Vasculitides can cause ION. 

Conal Lesions 

Conal abnormalities include, most commonly, thyroid 
eye disease (TED). Grave’s ophthalmopathy is another 
name for this entity. The muscles may be edematous, in- 
filtrated by lymphocytes, mucopolysaccharide, or fat. 
There may be exophthalmos, unilateral proptosis, in- 
creased orbital fat, injection of the fat, and exposed 
cornea. In TED, the inferior and medial recti are the most 
commonly enlarged muscles with sparing of the tendi- 
nous insertion. This finding is contrasted with the stereo- 
typical findings of pseudotumor of the orbit, which tends 
to affect the tendinous insertion of the muscles to the 
globe. Orbital pseudotumor is defined as a non-specific, 
idiopathic inflammatory condition for which no local 
identifiable cause or systemic disease can be found. Pain 
is an important feature of orbital pseudotumor. The 
histopathology can vary from polymorphous in inflam- 
matory cells and fibrosis, with a matrix of granulation 
tissue, eosinophils, plasma cells, histiocytes, germinal 
follicles and lymphocytes, to a predominantly lympho- 
cytic form. Pseudotumor may be classified as: (1) acute 
and subacute idiopathic anterior orbital inflammation; (2) 
acute and subacute idiopathic diffuse orbital inflamma- 
tion; (3) acute and subacute idiopathic myositic orbital 
inflammation; (4) acute and subacute idiopathic apical 
orbital inflammation; (5) idiopathic dacryoadenitis; and 
(6) perineuritis (optic nerve). 

The extraocular muscles, however, can also be affect- 
ed by adjacent inflammatory sinusitis or by lesions, 
which may cause venous congestion within the orbit. 
The latter may be seen in patients who have dural vas- 
cular malformations, cavernous carotid fistulae, orbital 
apex obstructions, or veno-occlusive disease. In this 
case, all of the extraocular muscles may be affected and 
there is usually injection of the fat due to the wide- 
spread edema. 

The extraocular muscles are striated muscle or of stri- 
ated muscle origin. Therefore, primary neoplasms of the 
muscle include rhabdomyosarcoma (Rh). Orbital Rh is 
the most common primary orbital malignancy in chil- 
dren. Clinically, its occurrence involves the differential 
diagnosis of acute and subacute proptosis of childhood. 
Rapidly progressive unilateral proptosis is the hallmark 
of orbital Rh. These tumors are capable of rapid growth 
and they have the potential to destroy orbital bones. The 
MRI features of these tumors are characteristic of long 
T1 and long T2 lesions (Fig. 2). There is significant con- 
trast enhancement on enhanced CT and MRI scans (Fig. 
2c). Rarely one sees lymphoma or metastases directly to 
the extraocular muscles. 




122 



M.R Mafee, D.M. Yousem 




Brown’s syndrome is a tenosynovitis of the tendon of 
the superior oblique muscle. This is identified on imag- 
ing as thickening of this muscular tendon. Clinically, the 
patients have restricted eye movement. 

Extraconal Space 

The majority of lesions in the extraconal space fall in the 
category of infectious and neoplastic etiologies. 
Lymphangiomas tend to populate the extraconal space. 
These are often multilocular cystic lesions that have a 
tendency to bleed. Orbital lymphangiomas occur in chil- 
dren and young adults. In contrast to rapid, self-limited 



growth of infantile capillary hemangiomas, lymphan- 
giomas gradually and progressively enlarge during the 
growing years. On MRI, lymphangiomas are hypointense 
or relatively hyperintense on T1 -weighted images and are 
usually very hyperintense on T2-weighted images. Fluid- 
fluid levels due to hemorrhage may be present. The le- 
sions do not enhance unless they also contain a heman- 
giomatous component. 

The most common infectious source of extraconal 
pathology is sinusitis. Sinusitis is also the most common 
cause of orbital cellulitis. The classification of orbital cel- 
lulitis includes five categories or stages of orbital in- 
volvement from sinusitis. These are: (1) inflammatory 
edema; (2) subperiosteal phlegmon and abscess; (3) or- 






Orbit and Visual Pathways 



123 



bital cellulitis; (4) orbital abscess; (5) ophthalmic vein 
and cavernous sinus thrombosis. Distinguishing between 
a phlegmon and a periosteal abscess is difficult, since rim 
enhancement of the periosteal abscess is rare in this lo- 
cation. What one sees is a low-density collection running 
parallel to the medial wall of the orbit, which displaces 
the extraocular muscles laterally. This is less commonly 
due to frontal sinusitis. Rarely one may see a small col- 
lection of air within the larger periosteal collection. There 
may also be injection of the fat and extraocular muscle 
enlargement as the infection proceeds through the orbit. 
The most dangerous of the infections to involve the orbit 
are those from Mucorales or Aspergillus, which can in- 
vade the vascular structures of the orbit leading to the 
cavernous sinus and internal carotid artery and conse- 
quent intracranial vascular complications (stroke, vas- 
culitis, sinus thrombosis). 

Traumatic lesions of the orbital wall also may form ex- 
traconal collections. These are usually hematomas that 
occur along the roof or the floor and medial orbital walls 
in association with blowout fractures. The muscles again 
are displaced inward by the extraconal collection. There 
may be associated swelling of the muscle or intraconal 
compartment. 

The bony orbit is also included in the extraconal tis- 
sue. Therefore, primary lesions of the bone such as mul- 
tiple myeloma, fibrous dysplasia, Paget’s disease and oth- 
er fibrochondroosseous lesions of the surrounding bone 
may present with orbital symptomatology. One classic 
finding is dysplasia of the greater wing of the sphenoid, 
which is found as a primary criterion for neurofibro- 
matosis type 1 . Often these patients present with pulsatile 
exophthalmos secondary to transmitted cerebrospinal flu- 
id (CFS) pulsations and intracranial pressure to the orbit 
since the bony protection is missing in the greater wing 
of the sphenoid. On plain films this may appear as an 
“empty orbit”. 

Another example of how the orbits may be affected by 
extraconal pathology is given by meningoencephalocele. 
Once again there is a defect in the orbital bony confines 
and CSF, meninges or brain may show mass effect on the 
orbital structures. 



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IDKD 2004 



Temporal Bone and Auditory Pathways 

J.W. Casselman 

Algemeen Ziekenhuis St. Jan Brugge, Brugge, Belgium 



Introduction 

Today the anatomy of the temporal bone can be evaluat- 
ed in detail. Computed tomography (CT) is the method of 
choice to look at the external ear and middle ear. But CT 
also provides much information about the inner ear. New 
CT equipment, using helical scanning and multidetector 
technology, enables us to scan the temporal bone in de- 
tail. Once the images are made, one can recalculate them 
even every 0.1 mm. On these very thin images, partial 
volume is no longer a problem and hence every tiny 
structure can be seen. Moreover, excellent multiplanar re- 
constructions can be made. Structures like the branches 
and footplate of the stapes and chorda tympani can now 
be evaluated in a reliable way. 

Magnetic resonance imaging (MRI) is used to look at 
the inner ear. Especially T2-weighted gradient echo (CISS) 
and turbo spin echo (DRIVE, FSE, FIESTA) sequences 
can be used. These images show the intralabyrinthine flu- 
id in detail and enable us to see the scala tympani and 
vestibuli separately inside the cochlea. Another advantage 
is that the facial nerve and the cochlear, inferior vestibular 
and superior vestibular branches of the eighth cranial nerve 
can all be distinguished on these images. Even the posteri- 
or ampullar nerve and the ganglion of Scarpa can today be 
seen on 0.7-mm images made every 0.35 mm, using a 
1024 matrix (Fig. 1). 

MRI is also the only technique that can visualise le- 
sions along the auditory pathway. Selective images 



Fig. 1. 1024 ma- 
trix, 0.7-mm DRI- 
VE image shows 
the posterior am- 
pullar nerve, origi- 
nating from the 
posterior wall of 
the inferior vestibu- 
lar nerve, and the 
separation in scala 
vestibuli and tym- 
pani inside the 
cochlea 



through the cochlear nuclei, trapezoid body, lateral lem- 
niscus, inferior colliculus, medial geniculate body and 
auditory cortex often detect the cause of deafness when 
the selective CT and MRI studies of the temporal bone 
are negative. 

As a general rule one can say that patients with con- 
ductive hearing loss (CHL) should be examined with CT, 
while patients presenting with sensorineural hearing loss 
(SNHL), vertigo or tinnitus should immediately get an 
MRI study. There are of course exceptions and in many 
cases both CT and MRI can be useful. In the following 
paragraphs, I discuss the most frequent indications to 
perform imaging of the temporal bone. For each indica- 
tion, the choice between CT and MRI is discussed. 

Otosclerosis 

In otosclerosis, the dense ivory-like endochondral bone 
layer around the labyrinthine capsule is replaced by foci 
of spongy, vascular, irregular new bone. The cause of this 
replacement is still under discussion. Patients with oto- 
sclerosis present with mixed hearing loss. However, the 
conductive component is most often predominant and the 
lesions are often only visible on CT. Hence CT is the 
method of choice. Otosclerosis (and otospongiosis) can 
be fenestral or retrofenestral. 

In fenestral otosclerosis, the promontory, facial nerve 
canal and oval and round windows are involved. The 
most frequent lesion is a hypodense area or even mass 
at the fissula ante fenestrum. These lesions can also oc- 
cur on the promontory or at the round window. At the 
level of the oval window, otospongiosis can block the 
anterior branch of the stapes so that they can no longer 
move freely, causing conductive hearing loss. 
Thickening of the footplate can also occur and has the 
same result. Lesions near the footplate are difficult to 
visualise, and a double oblique technique is needed to 
visualise both branches of the stapes and the footplate 
in one plane (Fig. 2). To achieve this, helical acquired 
images should be reconstructed every 0.1 mm so that 
double oblique images with sufficient quality are ob- 





Temporal Bone and Auditory Pathways 



125 




Fig. 2a-c. The only reliable way to evaluate fenestral otosclerosis 
is the double oblique technique, a Paracoronal images are made on 
the axial plane through the stapes, b Then, double oblique images 
are made when a reconstruction parallel to the incudostapedial 
junction on the paracoronal images is made, c The resulting dou- 
ble oblique image clearly shows otospongiosis (arrows) at the fis- 
sula antefenestrum, encasing the anterior branch of the stapes 



tained. The round window should always be checked, as 
some studies have shown that surgery of the stapes and 
oval window is less successful when the round window 
is obliterated. 

Retrofenestral otosclerosis involves the cochlea or the 
bone around the membranous labyrinth (with the excep- 
tion of the lateral wall of the labyrinth). A hypodense ring 
can develop around the complete cochlea and is then 
called “the fourth ring of Valvassori”. However, the le- 
sions can also be more subtle and frequently a small hy- 
podense spur can be seen anterior to the antero-inferior 
wall of the fundus of the internal auditory canal. 



Trauma 

Fractures of the temporal bone can best be seen on CT. 
Both longitudinal and transverse fractures can be distin- 
guished. Longitudinal fractures follow the long axis of 
the temporal bone, from the surface of the petrous-mas- 
toid bone to the middle ear cavity and geniculate gan- 
glion area and even petrous apex. Transverse fractures 
run perpendicularly on the long axis of the petrous bone 
and petrous apex and, hence, nearly always involves the 
inner ear. Post-traumatic CHL is most often explained by 
the CT findings. Post-traumatic obliteration of the mid- 
dle ear cavity and fractures or luxation of the ossicles can 
easily be recognized on CT today. However, CT some- 
times does not provide an explanation for post-traumatic 
SNHL and facial nerve palsy. In these cases, MRI of the 
temporal bone can often provide the answer, but CT is 
and remains the most important and first study in case of 
trauma. 

Unenhanced T1 -weighted images must be used to 
recognize post-traumatic intralabyrinthine haemorrhage 
which represents inner ear concussion. Cloth or fibrosis 
formation in the labyrinth can be excluded using thin 
T2-weighted images (DRIVE, CISS, FIESTA). The high 
signal intensity of the fluid disappears in case of fibro- 
sis or cloth formation; the fluid however keeps its nor- 
mal high signal intensity when it is mixed with fresh 
blood. Post-traumatic intralabyrinthine enhancement 
can also occur. When the trauma causes a leak of in- 
tralabyrinthine fluid towards the middle ear, the inner 



ear reacts with a higher fluid production to compensate 
the loss. This results in hyperaemia of the labyrinth and 
can, during the acute phase, sometimes be seen as en- 
hancement. 

Fractures through the tegmen can result in formation 
of meningocele or encephalocele. Blood or inflammation 
in the middle ear can only be distinguished from 
meningo- or encephalocele formation in a reliable way 
when MRI is performed. 

Finally, the cause of hearing loss can also be located 
along the auditory pathways. The most frequent struc- 
tures involved in trauma are the inferior colliculi (con- 
cussion when they are hit by the free edge of the tentori- 
um during trauma) and the auditory cortex (hit by over- 
lying bone or damaged by concussion or bleeding caused 
by the contrecoup). Again, these lesions are often only 
visible or their full extent is only visible on MRI. 

Facial nerve palsy is not always caused by a fracture 
running through the facial nerve canal (e.g. tympanic seg- 
ment). Therefore, sometimes CT shows normal results in 
patients with post-traumatic facial nerve palsy. The 
labyrinthine segment of the nerve is vulnerable because it 
occupies 95% of the available space of the canal. Hence, 
retrograde oedema can easily cause compression and sec- 
ondary necrosis of this facial nerve segment. This can be 
seen as enhancement of the labyrinthine segment and en- 
hancement near the fundus of the internal auditory canal, 
which is always abnormal. In such a case, decompression 
of the nerve should be considered in order to save the fa- 
cial nerve. 



Chronic Middle Ear Inflammation 

In chronic middle ear inflammation, middle ear aeration 
is often disturbed and hence the drum is frequently re- 
tracted and thickened. Moreover, mucosal thickening or 
even obliteration of the middle ear cavity by fluid and or 
thickened glue-like material can be present. Chronic in- 
fection can cause demineralisation of the ossicles; trac- 
tion on the ossicle can even cause luxation of the ossicles. 
However, clear destruction or displacement of the ossi- 
cles is not seen. Middle ear inflammation often follows 
pre-existing structures like the plicae and ligaments 
forming the tympanic diaphragm. Therefore, when mid- 
dle ear obliteration suddenly stops at these structures, 
forming a straight barrier with the aerated part of the rest 
of the middle ear, then one is nearly always dealing with 
inflammation. The diagnosis is more difficult if the com- 
plete middle ear and mastoid are obliterated. In this case, 
a small cholesteatoma can be hidden somewhere in the 
inflammation. In these patients, one should carefully 
check whether the bony septa between the mastoid and 
antral aerated cells are intact. If they are, one is probably 
dealing with inflammation; if they are not, cholesteatoma 
is suspected. Comparison of the bony septa of both ears 
helps to detect an underlying cholesteatoma. When the 
thickened drum or inflammatory tissue in the middle ear 




126 



Jan W. Casselman 



calcifies, then one is dealing with tympanosclerosis. It is 
obvious that only CT can depict these middle ear changes 
in a reliable way. 

Cholesteatoma 

Cholesteatoma is a sac lined by keratinizing, stratified, 
squamous epithelium trapped in the middle ear and grow- 
ing in the middle ear or mastoid. This lesion displaces the 
ossicles when it becomes large enough and also destroys 
the ossicles and walls of the middle ear cavity. Typically, 
the lateral wall of the middle ear cavity is eroded and the 
scutum is amputated. In the antrum and mastoid, the sep- 
ta between the different aerated cells are destroyed by the 
lesion. As cholesteatomas grow and become masses, they 
develop convex borders; this is however only visible 
when the surrounding part of the middle ear or mastoid 
is aerated. So, when a mass has two convex borders, it is 
likely to be a cholesteatoma; when one border is convex 
there is suspicion of a cholesteatoma. When only straight 
or concave borders are seen, one is probably dealing with 
inflarnmation. Again, CT is the method of choice to eval- 
uate the walls of the middle ear and the ossicles. The 
technique is also suited to check whether recurrent 
cholesteatoma is present and to help the surgeon decide 
whether to perform a second-look operation or a re-inter- 
vention. 

When the middle ear is completely obliterated on CT, 
it is often impossible to distinguish among post-surgery 
changes, inflammation and recurrent cholesteatoma. 
Moreover, when surgery has been performed previously, 
landmarks such as intact ossicles and walls of the middle 
ear cavity can often not be used, as they may already have 
been damaged by the original lesion or the previous 
surgery. In these cases, one often has no clue whether 
cholesteatoma is present or not. Today MRI plays an im- 
portant role in these patients. 

A cholesteatoma has rather specific signal intensities 
on MRI: high signal intensity (SI) on T2-weighted im- 
ages, low SI on unenhanced T I -weighted images, low SI 
on gadolinium-enhanced T1 -weighted images but with a 
thin rim of enhancement around the lesion, and high SI on 
diffusion-weighted MR images (b-IOOO). Hence, MRI 
can in most cases tell the surgeon which type of lesion 
will be found, obviating the need for surgery in many cas- 
es. The same goes for patients who were already operated 
and in whom a second-look operation is scheduled. 

Today MRI can be used to exclude recurrent 
cholesteatoma and can therefore avoid the second-look 
operation in many patients. There is, however, still a 
problem with partial volume effects as it is difficult to ac- 
quire diffusion-weighted MR images thinner than 3 mm. 
Hence, small recurrences can still be overlooked. On the 
other hand, there are no false positives on the diffusion- 
weighted MR images, which means that when high sig- 
nal intensity is present on b-1000 images, a 
cholesteatoma will be found (Fig. 3). 




Fig. 3a, b. Cholesteatoma in right middle ear and mastoid, a High 
signal intensity (SI) on coronal T2-weighted image (left) , low SI 
on coronal T1 -weighted image (middle), and low SI on axial 
gadolinium-enhanced T1 -weighted image but with rim enhance- 
ment (right), b High SI on b-1000 diffusion-weighted image 

Other lesions, such as a cholesterol granuloma, have 
specific signal intensities as well (high SI on both Tl- 
and T2-weighted images, low SI on diffusion-weighted 
images). Middle ear inflammation is typically hyperin- 
tense on contrast-enhanced T1 -weighted images. If doubt 
persists, “late-phase” images often show the enhance- 
ment better and then confirm that one is dealing with in- 
flammation (cholesteatomas do not enhance at all). 

Congenital Middle Ear Malformations 

Congenital malformations of the middle ear and external 
ear are linked embryologically and therefore are often 
both present in the same patient. CT is the method of 
choice to look for these congenital malformations, as air 
and bone are best seen on CT. In the middle ear, the sta- 
tus of the ossicles must be evaluated and described in de- 
tail, as surgeons need to know if the hearing loss can be 
caused by a malformation of the ossicles. If the ossicles 
are malformed, they want to know if enough ossicles are 
present to reconstruct a functioning ossicular chain. 
Moreover, they must know if normal, open round and 
oval windows are present. Detailed imaging is needed to 



Temporal Bone and Auditory Pathways 



127 



provide this information, and thin images (0.1 -mm re- 
constructions) are needed to see these often subtle mal- 
formations. When the external ear and middle ear are 
malformed, one must always check the position of the fa- 
cial nerve. The nerve often shifts anteriorly and runs 
through the middle ear cavity (Fig. 4); it can even split in 
2 or more mastoid branches. Hence, the nerve is at risk 
and therefore it is the task of the radiologist to warn the 
surgeon when the nerve has an abnormal course. The 
middle ear can of course not be evaluated when the ex- 
ternal auditory canal is absent or when an atresia plate is 
present. In these cases, the surgeon is completely depen- 
dent on the imaging findings, which indicate whether the 
external ear and ossicular chain can be reconstructed. 



Acoustic Schwannoma 

Acoustic schwannomas, the most frequent lesion found 
inside the internal auditory canal (lAC), can cause 
SNHL, vertigo and tinnitus. They can be detected on 
gadolinium-enhanced T1 -weighted images, however dif- 
ferentiation from neuritis can be difficult. Gradient echo 
T2-weighted images are used to distinguish both entities. 
In schwannoma, a nodular hypointensity is found in the 
course of the involved nerve, while in neuritis a normal 
or fusiform, thickened nerve is found. This applies espe- 
cially to facial nerve neuritis, as enhancement of the 
vestibulocochlear nerve (eighth nerve neuritis) is rarely 
seen. 

When the schwannoma is small, one can even distin- 
guish on which branch (cochlear, inferior vestibular or 
superior vestibular) of the eighth nerve it is located. 
Imaging studies showed that vertigo is more frequently 
correlated with small and strictly intracanalicular 
schwannomas. Clinical studies also showed that purely 
intracanalicular acoustic schwannomas result in earlier 
onset of vestibular symptoms. 




Fig. 4. Coronal CT image shows aplasia of the external auditory 
canal and bony atresia plate with fixation of the fused ossicles. The 
facial nerve decends in the middle of the middle ear cavity 



Once the diagnosis of schwannoma is made, the 
growth potential of the lesion must be assessed. This is 
best achieved using 1-mm T1 -weighted gradient echo im- 
ages (e.g. 3DFT-MPRAGE) on which volume measure- 
ments are performed. In the first year, follow-up studies 
should be acquired every 6 months and subsequently an- 
nually in case the schwannoma is not growing fast. 

Once it is decided that a schwannoma must be re- 
moved, one must determine if hearing preservation 
surgery is possible. Here, imaging plays a key role today. 
First, the presence of fluid between the schwannoma and 
the fundus of the lAC must be assessed. If fluid is still 
present, the surgeon can stay away from the base of the 
cochlea and a suboccipital or middle cranial fossa ap- 
proach can be used, therefore preserving hearing func- 
tion. If no fluid is left, the surgeon has to drill in the 
cochlear canal, and the patient becomes deaf; therefore, 
the less invasive translabyrinthine approach is chosen in 
these patients. 

Another important sign is the signal intensity of the 
cerebrospinal fluid (CSF) between the schwannoma and 
fundus of the lAC, as well as the signal intensity of the 
intralabyrinthine fluid . Normal signal intensity of these 
fluid spaces seems to correlate well with good results af- 
ter hearing preservation surgery. However, when the sig- 
nal intensity of the fluid is decreased, the success of hear- 
ing-preservating surgery is significantly worse (Fig. 5). 

Labyrinthitis 

Only “end-phase” ossifying labyrinthitis is visible on CT. 
Acute labyrinthitis (seen with gadolinium enhancement) 
and subacute labyrinthitis (fibrosis formation, only seen 
on TSE or GE T2-weighted images) are only detectable 
on MRI. Therefore, MRI is the method of choice to ex- 
amine these patients. Moreover these patients present 
with sensorineural hearing loss, which also directs them 




Fig. 5. Axial 0. 7-mm gradient echo T2-weighted MR image. The 
signal intensity inside the left labyrinth is decreased, which is a bad 
predictor for success following hearing preservation surgery 





128 



Jan W. Casselman 



towards an MRI examination. However, when the high 
signal intensity of fluid is lost on T2-weighted TSE or GE 
images, one cannot differentiate between fibrosis and os- 
sification. A combination of MRI and CT is needed to get 
a complete picture of the labyrinthitis. 

Labyrinthitis is most often viral. In these cases, 
gadolinium enhancement is seen but the fibrosis forma- 
tion and ossification are most often not present. In case of 
meningococcus or pneumococcus infection (meningitis), 
it is a different story. Fibrosis develops quickly and calci- 
fication can already appear in 3-4 weeks. Meningitis oc- 
curs of course most frequently in children; when both ears 
are affected complete deafness can be the consequence. 
The only solution for these children is to install a cochlear 
implant as soon as possible, before labyrinthine fibrosis 
and ossification occur. As this can happen very fast, CT 
and MRI have to be performed quickly and this indication 
must be considered an emergency. Scheduling such a pa- 
tient 1-2 weeks later can result in permanent deafness. As 
most of these children are examined under anaesthesia, it 
is wise to perform CT and MRI at the same time in order 
to avoid a second anaesthesia, with its associated risks, in 
case MRI or CT alone cannot give all the answers. 



Congenital Inner Ear Malformations 

Patients with inner ear malformations present with “con- 
genital” sensorineural hearing loss. The bony inner ear 
malformations can be seen on CT but these malforma- 
tions are better seen on MRI. Only MRI can be used to 
evaluate if fluid is still present inside the malformed 
labyrinth, and can also distinguish the scala tympani and 
vestibuli in a reliable way. Moreover MRI can also be 
used to check whether a normal cochlear nerve is present 
(Fig. 6). If the vestibulocochlear nerve or cochlear branch 
of this nerve is absent, then cochlear implant surgery can 
no longer solve the problem and an unnecessary expen- 
sive intervention can be avoided. 




Fig. 6a, b. Congenital deafness on the left side due to absence of 
the cochlear branch of the eighth cranial nerve in an otherwise 
normal left inner ear. a Both the cochlear and inferior vestibular 
branch of the Vlllth nerve can be seen in the right internal audito- 
ry canal, b On the left side the cochlear branch is absent and hence 
no nerve can be seen near the base of the cochlea 



More frequent inner ear malformations are an enlarged 
endolymphatic duct and sac (enlarged vestibular aque- 
duct) and a saccular lateral semicircular canal. The latter 
most often has no elinical consequences. An enlarged en- 
dolymphatie duct and sac is, however, linked with SNHL 
and frequently intraeoehlear ehanges are present. 

The danger of a “gusher ear” is always present when in- 
ner ear malformations are deteeted. The absence of a nor- 
mal bone barrier between the fundus of the internal audi- 
tory eanal and the base of the coehlea (very likely) and the 
presenee of a large vestibular aqueduet (less likely) are 
signs that should warn the surgeon of a potential gusher 
ear. In a gusher ear, the CSF pressure is transmitted to the 
intralabyrinthine fluid. When the surgeon operates on the 
oval window and footplate, the fluid can gush out of the 
oval window and a completely deaf ear will result. Henee, 
it is important to warn the surgeon if one of these suspi- 
cious signs is seen. Unfortunately, gusher ears ean occur 
in inner ears that are radiologieally completely normal. 



Pathology Involving the Central Auditory 
Pathways 

When SNHL is present, the pathology is frequently loeated 
along the auditory pathways. In these patients, seleetive CT 
and MRI studies are normal. Therefore, MRI is the method 
of choiee in these patients and selective inner ear MRI 
should always be completed by a brain study. The cochlear 
nuclei, trapezoid body, lateral lemniscus, inferior eollieulus, 
medial geniculate body and auditory eortex can all be af- 
feeted. Infarctions (in older patients), multiple selerosis (in 
younger patients), trauma, tumour and inflammation can af- 
fect these structures and cause sensorineural hearing loss. 
Congenital malformation (pachygyria or polymicrogyria) 
can even be present in the auditory cortex and should be 
checked in all cochlear implant candidates. 



Tinnitus 

Patients with pulsatile tinnitus ean today be examined non- 
invasively with MRI. Patients with subjective and nonpul- 
satile tinnitus ean also be examined using magnetie reso- 
nance angiography (MRA) but the diagnostic yield is much 
lower. Neurovascular conflicts near the root entry zone of 
the facial and vestibulocochlear nerves can best be recog- 
nised on gradient echo T2-weighted images. These images 
ean also be used to provide the surgeon with virtual images 
of the confliet in the eerebellopontine angle (CPA). Vascular 
time of flight (TOF) images can be used to identify the ves- 
sel causing the eonflict or to differentiate between arteries 
and veins (nonenhanced and gadolinium-enhanced images). 
However, neurovascular conflict is not the most frequent 
cause of pulsatile tinnitus at all. Paragangliomas, dural arte- 
riovenous fistulas, idiopathic venous tinnitus and benign in- 
tracranial hypertension are the most frequent causes, and 
only the first two pathologies can be shown on MRI. 





Temporal Bone and Auditory Pathways 



129 





Fig. 7a, b. Dural fistula, a The 
unenhanced time of flight 
(TOP) MRA image shows in- 
creased flow velocity in the area 
of the superior petrosal sinus, 
b Selective reconstructed maxi- 
mum intensity projection (MIP) 
image shows that an occipital artery branch, PICA, AICA and 
branches from the superior cerebellar and posterior cerebral arter- 
ies are feeding the fistula 



Dural fistulas (Fig. 7) causing early venous drainage 
can be detected on nonenhanced images. Glomus tu- 
mours, arteriovenous malformations, aberrant vessels 
running through the middle ear, high or dehiscent jugular 
bulbs, tortuous carotid arteries near the skull base, fibro- 
muscular dysplasia and carotid dissection can be detect- 
ed on both unenhanced and gadolinium-enhanced MRA 
images. Vascularised tumours such as meningiomas 
cause higher arterial and venous flows in their surround- 
ings and therefore can cause tinnitus. This is why tumours 
in the neighbourhood of the temporal bone must be ex- 
cluded in these patients. Finally, CT is sometimes neces- 
sary to find the cause of tinnitus, for example in the case 
of Paget’s disease. However, MRA has become the 
method of choice because it is more successful than CT 
in detecting the causes of tinnitus. Angiography is only 
used in treatment (e.g. embolisation) or for diagnosis 
when pulsatile tinnitus renders a normal life impossible 
and MRI and CT remain negative. 



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IDKD 2004 



Imaging the Temporal Bone 

F. Veillon, S. Riehm 

Service de Radiologie 1, University of Strasbourg, Strasbourg, France 



Anatomy, How Reading Imaging 

Imaging of the temporal bone must be integrated into the 
clinical context because the information provided by otol- 
ogists is of great interest. The temporal bone contains 
three cavities: two are filled with air (external ear and 
middle ear) and one contains fluid (inner ear, or 
labyrinth, connected to the brain by the eighth cranial 
nerve). The aims of imaging are, in all pathologies, to 
avoid surprises during surgery of the middle ear and to 
provide information about the morphology of the cavi- 
ties, in particular the inner ear and internal auditory mea- 
tus. The procedures for analyzing the different structures 
of the temporal bone on diagnostic images are the same, 
and regard both the content and the walls of the cavities. 

Regarding the external ear, the content of the external 
auditory meatus is easily analyzed at otoscopy. However, 
the adjacent regions, including the temporomandibular 
joint (TMJ), lateral pharyngeal area, and third portion of 
the facial nerve, have to be shown by imaging. 

The middle ear contains mucosa, the auditory ossicles, 
tendons, ligaments and, in pathological cases, also soft 
tissue. The radiologist must analyze the different walls of 
the middle ear: 

- The bony roof, separating the middle ear from the du- 
ra, the cerebrospinal fluid (CSF) and the brain; 

- The floor, with the passage of the jugular vein; 

- The external wall, made of the tympanic membrane 
(drum) and the squamous bone; 

- The posterior wall, with the facial nerve and the pos- 
terior petrous cells; 

- The anterior wall, bordered by the internal carotid 
artery, the eustachian tube below and the middle cra- 
nial fossa above; 

- The inner wall, containing the round and oval windows 
and abutting on the lateral semicircular canal and the 
second part of the facial nerve. 

Imaging analysis of the inner ear considers the size, 
shape and structure of the otic capsule, as well as the na- 
ture of the fluid contents of the cavity. Furthermore, we 
must evaluate the walls of the internal auditory meatus, 
its contents (fluid and the seventh and eighth cranial 
nerves), and the nature of the canals in its fundus. 



Imaging Techniques 

The radiologist has two techniques for analyzing the dif- 
ferent cavities of the temporal bone: spiral computed to- 
mography (CT) and magnetic resonance imaging (MRI). 
Both techniques are useful for imaging the external, mid- 
dle and inner ears, and the internal auditory meatus, de- 
pending on the clinical context. 

Spiral CT with a 16-row detector provides good im- 
ages of the cavities and canals of the temporal bone. In 
our experience, the slices should be 0.6-mm thick, with 
an overlap of 0.2, 0.5 or 0.7 mm, depending on the cho- 
sen plane. Magnification of the windows is useful. The 
lateral semicircular canal is parallel to the axial imaging 
plane. Imaging in the frontal (coronal) plane is always 
performed; the sagittal plane is used in cases of trauma 
or malformation, after middle ear surgery, and for all 
pathologies of the external auditory meatus. 

The choice of MRI protocol depends on the cavity to 
be analyzed: 

- External auditory meatus. The main pathology for 
which MRI is needed is external malignant otitis media, 
an infection of the external ear and its adjacent regions. 
The best sequence consists of gadolinium-enhanced, 
fat-saturated T1 -weighted images in the horizontal (ax- 
ial) plane with 1- or 2-mm sections parallel to the roof 
of the orbit and centered on the temporal bone. 

- Middle ear. MRI is useful for the evaluation of the soft 
tissue content. The most appropriate protocols consist 
of T1 -weighted imaging without and with gadolinium 
enhancement and diffusion-weighted imaging in the 
axial or frontal plane. Frontal T2-weighted images are 
useful for analyzing the relationships of the middle ear 
with the dura mater, CSF and brain. High-resolution 
T2-weighted images provide further information about 
the fluid or solid contents of the middle ear. Actual 
slice thickness (0. 5-0.9 mm) depends on the scanner. 
The field of view must be small (10x10 cm^), and the 
matrix is 256x256. 

- Inner ear. T1 -weighted images without and with 
gadolinium enhancement in the axial plane parallel to 
the roof of the orbit (1- or 2-mm sections) provide in- 
formation about the content, size and shape of the 




Imaging the Temporal Bone 



131 



labyrinth. High-resolution T2-weighted images offer 
more precise information about the shape of the 
labyrinth and its fluid contents. 

- Internal auditory meatus. T1 -weighted images without 
and with gadolinium enhancement, possibly with fat 
saturation, and high-resolution T2-weighted images are 
appropriate for analyzing the signal of the CSF, and the 
size and shape of the seventh and eighth cranial nerves. 

Temporal Bone Pathologies 

Inflammation 

In emergency situations of mastoiditis, CT is necessary 
for determining the integrity of the middle ear and inner 
ear walls, which may be destroyed. CT with contrast 
medium is always necessary if MRI is not planed for the 
search for a lateral sinus thrombosis, meningitis, or an 
abscess outside or inside the adjacent brain. 

Tympanosclerosis, a frequent pathology of the middle 
ear, consists of the calcification of the soft tissue, liga- 
ments or tendons. CT is of particular importance in eval- 
uating the amount of calcification and the possible block- 
age of the ossicles. The stapes is often highly calcified, 
with increased thickness of the footplate. As in all chron- 
ic forms of otitis media, there may be destruction of the 
ossicles, particularly the long process of the incus. 

Imaging is never requested in the evaluation of hyper- 
plasia. Nevertheless, the radiologist must know its CT and 
MRI presentations, for it is often associated with 
cholesteatoma. Hyperplasia often appears as an increased 
thickness of the mucosa of the tympanic cavity. It may fill 
up the whole middle ear. If a suspicion of cholesteatoma 
remains doubtful on CT, an MRI examination is necessary 
for the differential diagnosis: a keratoma appears gray in 
signal on T1 -weighted images, while hyperplasia shows 
peripheral enhancement on gadolinium-enhanced images. 

\^en visible at otoscopy, granulomas appear as blue- 
red masses. At CT they are bowl-shaped; at MRI, they are 
white (hyperintense) on Tl- and T2-weighted images, and 
show no enhancement after gadolinium administration. 

Fibrosis may totally fill an operated cavity of the tem- 
poral bone. It appears as a gray, soft-tissue area on CT 
images. The diagnosis is only possible with MRI: fibro- 
sis appears gray (isointense to the cerebellum) on unen- 
hanced Tl -weighted images and hyperintense on Tl- 
weighted images 45 min after gadolinium administration. 

Cholesteatoma complicates a retraction with a perfora- 
tion of the drum in most cases. It is white at otoscopy but 
not always completely visible if the extension is located in 
the attic. At CT, the typical aspect is the one of a rounded 
mass in the external part of the attic with destruction of the 
scutum. The extension may be important throughout the 
tympanic cavity and in the antrum (Fig. 1). In rare cases, 
it is associated with destruction of the posterior wall of the 
petrous bone; the dura is never destroyed. The ossicles can 
be normal or partially or totally destroyed. The labyrinthine 



bone is eroded in 5%-10% of cases, and in the majority 
of cases it is open to the lateral semicircular canal. While 
the extent of tumor is not so well evaluated by CT, partic- 
ularly when the keratoma totally fills the cavity, MRI can 
provide good information. The lesion appears gray on 
Tl -weighted images, does not enhance after gadolinium 
injection, and morphologically consists of a round or oval 
mass with a ring of hyperplasia (Fig. 2). When a fistula is 




Fig. 1. Frontal view of a cholesteatoma at computed tomography. 
7, cholesteatoma-, 2, destruction of the scutum; 3, fistula of the su- 
perior semicircular canal 




Fig. 2. Axial Tl -weighted MR image of cholesteatoma after 
gadolinium administration. 1, cholesteatoma; 2, rim of enhance- 
ment in the surrounding hyperplasia; 3, inflammation in the squa- 
mous cells with enhancement 




132 



F. Veillon, S. Riehm 




Fig. 3. Axial diffusion-weighted image of cholesteatoma. 1, 
petrous bone; 2, posterior cranial fossa; 2, fourth ventricle; arrows, 
hyperintense signal of the cholesteatoma 



suspected at CT, high-resolution T2-weighted MR images 
can evaluate the extension to the perilabyrinthine compart- 
ment. On diffusion-weighted images, cholesteatoma has a 
high signal (Fig. 3). 

Malformations 

The bony external auditory meatus may be small or ab- 
sent, rendering the examination of the middle ear diffi- 
cult. When imaging the middle ear for possible malfor- 
mations, the main interest regards the careful evaluation 
of the ossicles, since conductive hearing loss can be suc- 
cessfully treated surgically, provided that the facial nerve 
is spared. CT can evaluate the presence, absence, fusion 
or fixation of the ossicles. The anatomy of the windows 
(normal, small or absent) must always be determined 
(Fig. 4). 

Malformations of the inner ear are common. The ma- 
jority consists of small or more important deformities of 






Fig. 4a-d. Malformation 
of the round windows, a, 
b Stenosis of both round 
windows {arrows) in the 
axial plane, c, d Frontal 
views: absence of access 
to the membrane of the 
round windows {arrows) 








Imaging the Temporal Bone 



133 




Fig. 5a, b. Malformation of the inner ear. a Dilatation of the vestibule and lateral and posterior semicircular canals, b Dilatation of the lat- 
eral semicircular canal (7) and of the vestibule (2) 



the posterior labyrinth (Fig. 5). The second most common 
abnormality is dilatation of the aqueduct of vestibule, 
which contains the dilated endolymphatic canal. 
Dilatation and abnormality of the cochlea, with or with- 
out a dilated aqueduct of vestibule, is a third common ab- 
normality. Segmentation of the cochlea may be abnormal; 
this is better demonstrated by MRI than by CT. Again, 
analysis of the windows is important. CT and MRI are 
complementary examinations in the study of the inner ear 
malformations: the shape of the labyrinth is analyzed by 
both imaging modalities, the windows are best imaged 
with CT, and the content of the labyrinth is best studied 
using MRI. 

CT reveals deformities of the canals in the fundus of 
the internal auditory meatus, and demonstrates when the 
modiolus is absent in cases of suspected gusher syn- 
drome. In other cases, the problem is to analyze the pres- 
ence and size of the auditory nerve on MRI. Sagittal Tl- 
weighted sections are important for this evaluation. 

Imaging is necessary before cochlear implantation. CT 
is used to evaluate the ventilation of the tympanic cavity, 
the presence of an open round window, and possible cal- 
cifications in the labyrinth. MRI helps in the evaluation of 
the fluid contents of the labyrinth, the size of the audito- 
ry nerve, and the nature of the cochlear pathways in the 
brain. It is important to use both imaging modalities to 
evaluate the integrity of the labyrinthine lumen. 

Otosclerosis 

In otosclerosis, a common inner ear pathology, the 
labyrinthine bone is replaced by areas of spongy bone (oto- 
spongiosis). Usually, the small focus of otosclerosis is lo- 



cated close to the anterior part of the oval window (Fig. 6). 
In 10% of cases, the round window is also abnormal. The 
whole labyrinthine capsule may be involved by the otoscle- 
rotic process. Surgery is the usual treatment, with place- 
ment of a prosthesis on the oval window. CT confirms the 
diagnosis and assists in the evaluation of the round window 
(the surgical results are not so good if the round window is 




Fig. 6. Otosclerosis. 1, otosclerosis (hypodensity); 2, otic capsule; 
S, vestibule; 4, internal auditory meatus; 5, anterior crus of the 
stapes; 6, posterior crus of the stapes; 7, footplate 






134 



F. Veillon, S. Riehm 



involved), the extension to the labyrinthine capsule, the po- 
sition of the facial nerve above the oval window, and the 
length of the long process of the incus. CT allows surgeons 
to analyze the position and length of the prosthesis after im- 
plantation. Rare post-surgical complications, particularly a 
granuloma of the perilabyrinthine space, may appear; MRI 
is the best examination to study this process. 

Trauma 

Trauma to the temporal bone is frequent. In 88% of cases, 
fractures run in the middle ear through the squamous or 
petrous bone and may involve the tympanic bone (Fig. 7); 




Fig. 7. Trauma of the petrous bone (axial CT section). Longitudinal 
extralabyrinthine fractures of the squamous bone {arrows) 



the ossicles may be displaced or fractured. CT in the three 
imaging planes helps analyze the outcome of trauma and 
the condition of the ossicles. In 7% of cases, trauma in- 
volves only the labyrinthine bone, with a fracture running 
in the inner ear (Fig. 8). Again, CT is useful for this analy- 
sis, while high-resolution T2-weighted MR images help 
evaluate the content of the labyrinthine lumen. This point 
is quite important if no fracture is visible at CT. In 5% of 
cases, the fracture is tympanolabyrinthic and involves the 
middle ear and inner ear, usually through the windows. A 
fistula of perilabyrinthine space is then common. If no 
fracture is demonstrated in a patient with post-traumatic 
vertigo, tinnitus and hearing loss, MRI (particularly T2- 
weighted imaging) is necessary for evaluating the auditory 
and vestibular systems in the brain. 

Temporal Bone Tumors 

In the external auditory meatus, the most common 
pathology is pseudotumoral malignant otitis media; in di- 
abetic patients this condition is usually due to infection 
with Pseudomonas aeruginosa. CT and MRI are per- 
formed to evaluate the extension of the inflammatory 
process. Carcinoma of the external auditory meatus is 
rare; the destruction and invasion of the adjacent regions 
are revealed by CT and MRI. 

Among tumors affecting the middle ear, glomic tumor 
is a common lesion that originates close to the inner wall 
of the middle ear along the inferior tympanic nerve 
(Jacobson’s nerve). It appears at otoscopy as a red, round- 
ed mass; on both CT and MRI, the lesion enhances after 
contrast medium injection. The position of the mass and 
its extension to the eustachian tube along the carotid 
canal, in the hypotympanum, are important to evaluate. A 
jugulotympanic tumor originating in the wall of the jugu- 
lar vein may invade the tympanic cavity; this tumor 




Fig. 8a, b. Trauma of the temporal bone, with translabyrinthine fracture, a Axial CT image. 7, fracture of the otic capsule; 2, fracture 
of the promontory; 3, middle ear without blood effusion, b Magnified axial CT image. 7, translabyrinthine fracture; 2, tympanic facial 
nerve; 5, vestibule 






Imaging the Temporal Bone 



135 



shows strong enhancement on CT and MR images after 
contrast medium injection. Primitive cholesteatoma is a 
rare lesion related to some rests of epidermoid tissue left 
in the middle ear. Usually it is small and located in the 
mesotympanum, not in the attic, like a secondary ker- 
atoma. The mass is white and visible at otoscopy; it ap- 
pears rounded at CT. There is no need for MRI if the ker- 
atoma is small. The destruction is usually limited. Other 
tumors (adenoma, carcinoid, meningioma, neuroma) are 
rare in the middle ear. 

The inner ear may be eroded or destroyed by tumors 
of the adjacent regions: apex, jugular foramen, internal 
auditory meatus. One tumor, the papillary tumor of the 
endolymphatic sac, originates in the inner ear lumen. 
This mass originates in the aqueduct of vestibule and 
leads to destruction of the inner wall of the petrous 
bone, with extension to the cerebellopontine angle and 
the middle ear. The mass is hyperintense on Tl - and T2- 
weighted images and shows heterogeneous contrast en- 
hancement. It is frequent in patients with von Hippel- 
Lindau disease. The primitive cholesteatoma of the in- 
ner ear is commonly located in the otic capsule or apex. 



with or without facial palsy. The signal on MR images 
is not different from that of secondary keratoma of the 
middle ear. 



Conclusions 

CT and MRI are of a great importance in imaging the 
pathology of the temporal bone. These techniques allow 
the otologist to choose between conservative or surgical 
treatment. In the case of surgery, imaging helps the sur- 
geon choose the surgical approach to the cavities and dis- 
cuss the expected clinical results after surgery with the 
patient. 



Suggested Reading 

Swartz JD, Hamsberger HR (1998) Imaging of the temporal bone. 
Thieme, New York Stuttgart 

Veillon F, Riehm S, Enachescu B, Haba D, Roedlich MN, Greget 
M, Tongio J (2001) Imaging of the windows of the temporal 
bone. Semin Ultrasound CT MR 22:271-280 




IDKD 2004 



Imaging the Pharynx and Oral Cavity 

B. Schuknecht^, A.N. Hasso^ 

^ Department of Neuroradiology, University Hospital, Zurich, Switzerland 
^ University of California, Irvine Medical Center, Orange, CA, USA 



Introduction 

Both magnetic resonance imaging (MRI) and computed 
tomography (CT) are commonly used to evaluate the up- 
per aerodigestive tract formed by the pharynx and oral 
cavity. Spatial anatomical descriptions of the head and 
neck structures are well suited to the axial and coronal 
sections provided by MRI and CT. These techniques are 
helpful for detecting lesions in clinical blind spots such 
as the submucosal spaces and the skull base and provide 
a more useful basis for differential diagnosis of patho- 
logical entities than the traditional descriptions based up- 
on the triangles of the neck. 

MRI Applications in the Head and Neck 

Receiver Coils 

Because of inherently poor signal-to-noise ratio (SNR) in 
the head and neck area, dedicated surface or phased-ar- 
ray coils are often needed to boost signal to acceptable 
levels. In a phased-array coil, data are combined to form 
a composite image. In general, the smallest possible coil 
that fits the anatomical region is recommended. Arrays of 
detection coils have recently been used to encode spatial 
information as well as to receive the MR signal. 
Simultaneous detection of spatial harmonics (SENSE) 
and simultaneous acquisition of spatial harmonics 
(SMASH) are parallel imaging techniques that take ad- 
vantage of the geometry of a coil array to encode multi- 
ple lines of MR image data simultaneously. In this way, 
scan time can be reduced by an integral factor up to 6 in 
both basic and advanced sequences such as contrast-en- 
hanced magnetic resonance angiography (MRA) and 
echo-planar imaging (EPI). 

Gadolinium Contrast Agents 

Unlike iodine, gadolinium (Gd) contrast agents do not 
produce a signal directly. Rather, they shorten both T1 
and T2 relaxation times of nearby mobile protons. Since 



T1 relaxation times are much longer than T2, gadolinium 
is a preferentially T1 -enhancing agent. Gd contrast agents 
have pharmacokinetics and volumes of distribution simi- 
lar to iodinated contrast agents. Unlike free Gd, gadolin- 
ium chelated with DTPA, DTPA-BMA, HP-D03 A, BOP- 
TA or DOTA is a non-toxic product that allows for rapid 
renal excretion. MRI contrast agents rarely cause side ef- 
fects, nephrotoxicity, or anaphylactoid reactions. 
Dynamic images can be obtained and tissue perfusion 
can be visualized with fast gradient echo techniques after 
power injection of the contrast agent, as it sequentially 
distributes intravascularly and extracellularly [1]. 
Hypervascularized lesions (e.g. paraganglioma, metasta- 
tic thyroid carcinoma) and normal tissue differ in contrast 
kinetics and therefore may be distinguished from 
metastatic cervical lymphadenopathy, edema, inflamma- 
tion, necrosis and fibrosis, which enhance late due to 
their larger interstitial spaces. 

Superparamagnetic Iron Oxide Particles 

MR lymphography with gadolinium chelates or novel ul- 
tra-small superparamagnetic iron oxide particles (SPIO) 
is beginning to show promise. Normal lymph nodes take 
up SPIO and have reduced signal intensity on post-con- 
trast T2- or T2*-weighted sequences due to magnetic sus- 
ceptibility effects. Nodal metastases do not show signal 
changes on post-contrast T2- or T2*-weighted scans. 
Early clinical experience suggests that SPIO-enhanced 
MR lymphography improves the sensitivity and speci- 
ficity for the detection of nodal metastases and may be 
helpful in presurgical planning [2]. 



CT Applications in the Head and Neck 

Multislice spiral CT offers increased temporal and spa- 
tial resolutions and thus allows dynamic volume scan- 
ning. Collimation is in the range from 0.75 to 1.0 mm, 
calculated slice thickness varies between 0.75 for a 16- 
row scanner and 1 .25 mm for a 4-row scanner, and the 
corresponding slice increment is between 0.5 and 0.7 




Imaging the Pharynx and Oral Cavity 



137 



mm. The table feed is 3.5 mm/rotation for a 4-row scan- 
ner (rot time, 0.5 s) and 8 mm for a 16-row detector 
scanner (rot time, 0.75 s), leading to scan times of 30 s 
and 25 s, respectively, to cover 20-22 cm from the orbital 
roof to the sternoclavicular junction. This protocol cov- 
ers the primary locations of head and neck tumors, in- 
cluding potential sites of spread like the skull base and 
cavernous sinus, and delineates lymph node levels from 
the skull base to the jugulum. 

Variations in the aforementioned protocol primarily af- 
fect scan times and therefore require careful adjustment 
of the amount and flow rate of contrast medium. In a typ- 
ical protocol, the flow rate is 2 ml/s, the acquisition is 
started following injection of 80 ml contrast medium, and 
the remaining 20 ml is injected during the subsequent 
scan and pushed with 20 ml of saline. With the exception 
of acute trauma and thyroid carcinoma, administration of 
nonionic contrast medium (iodine, 300 mg/ml) is virtual- 
ly always required in head and neck CT. 

Imaging of the carotid and vertebrobasilar arteries, 
either targeted with a limited scan range or from the 
aortic arch to the circle of Willis, has become feasible 
using a 4- or 16-row scanner [3]. Delineation of supra- 
aortic vessels is feasable using 40 ml contrast medium 
at a higher concentration of iodine (400 mg/ml) with an 
injection rate of 4 ml/s and a table feed of 18 mm/rota- 
tion. Recognition of vessel involvement by the primary 
tumor or metastatic lymphadenopathy and visualization 
of particular external carotid artery branches allow pre- 
cise noninvasive surgical planning of tumor resection 
as well as reconstruction by microvascular anasto- 
mosed flaps. 

Imaging of head and neck vessels is based on a vol- 
ume-rendering technique (VRT). Morphologic imaging 
uses multiplanar reconstructions (MPR) with 3 -mm con- 
tiguous slices in the axial and coronal planes [4]. 
Additional sagittal slices are required in lesions derived 
from the nasopharynx, base of the tongue, and posterior 
wall of the oro- and hypopharynges, and in cases of lev- 
els III-V lymph node involvement. Biplanar (axial and 
coronal) high-resolution bone window algorithm images 
are particularly useful in detecting involvement of the 
skull base and mandible; sagittal images are required to 
detect infiltration of the prevertebral fascia or vertebral 
column by neoplasm or inflammation. 

MRI of the Upper Aerodigestive Tract 

The key to interpreting the structures of the aerodiges- 
tive tract is the differences in MR signal intensity on var- 
ious pulse sequences. T1 -weighted images outline the 
musculofascial anatomy best (Fig. la). T2-weighted im- 
ages readily distinguish between mucosal structures and 
superficial adenoidal tissues. Mucosal and adenoidal tis- 
sues have a slightly prolonged T1 signal and a signifi- 
cantly prolonged T2 signal in comparison with muscle 
and fibrous tissues. The lingual tonsils are seen as U- 



shaped structures with high signal intensity, located at 
the base of the tongue. Pasavant’s ridge is a U-shaped 
mucosal band formed by the levator and tensor veli pala- 
tini muscles that insert laterally on the hard palate. This 
ridge functions as a sphincter during swallowing. The 
soft palate, the pharyngeal constrictor muscles, and the 
levator and tensor veli palatini muscles form a region of 
low signal intensity surrounding the airway at the level 
of the soft palate [5, 6]. 

T1 -weighted MR sequences allow good fat-muscle 
contrast, while T2-weighted sequences afford good dif- 
ferentiation between muscle and lymphoid tissue. The 
lymphoid tissues of the palatine or lingual tonsils have 
a slightly more intense signal than muscle on Tl- 
weighted images and a much more intense signal than 
muscle on T2-weighted images [7]. If the lymphoid tis- 
sues are hypertrophic, this signal may be similar to that 
of surrounding fat. Significant enhancement following 
contrast medium administration is deemed secondary 
to capillary permeability resulting from chronic in- 
flammation of the lymphoid tissues (Fig. lb). The pala- 




Fig. 1. Carcinoma of the right tonsil, a Top Tl-W image. The sig- 
nal intensity of the tumor in the right tonsil is incorporated into the 
signal from the adjacent muscles and lymphoid tissues in 
Waldeyer’s ring, b Bottom Tl-W image following gadolinium con- 
trast administration. Note that enhancement in the tumor in the 
right tonsil helps to clearly demarcate its margins from the mus- 
cles, but not from the lymphoid tissues. 




138 



B. Schuknecht, A.N. Hasso 



tine tonsils are the only component of Waldeyer’s ring 
that have a capsule which is low in signal compared to 
the high signal of parapharyngeal fat on T1 -weighted 
images. 

The combination of minor salivary glands mixed with 
fat results in a heterogeneous appearance of the palate 
on T1 -weighted images and increased signal on T2- 
weighted images. The median glossoepiglottic fold and 
the lateral pharyngoepiglottic folds are hyperintense on 
T1 -weighted images, as is the remaining pharyngeal 
mucosa [8]. 

T1 -weighted images achieve the best contrast between 
a tumor (intermediate signal) and the loose areolar tissue 
of the preepiglottic and paraglottic spaces. On T2- 
weighted images, a tumor may be hyperintense in com- 
parison to the intermediate signal of the surrounding are- 
olar tissues. 

Benign Lesions of the Pharynx 

Benign lesions of the pharynx may be epithelial (e.g. pa- 
pilloma, adenoma) or mesenchymal (e.g. hemangioma, 
angiofibroma, chondroma, chordoma) in origin, or may 
derive from specialized tissues (e.g. teratoma, cranio- 
pharyngioma, paraganglioma) [9-11]. 

Juvenile Nasopharyngeal Angiofibroma 

Angiofibromas are benign, locally aggressive, nonen- 
capsulated vascular tumors that arise in adolescent 
males. These tumors are typically located in or near the 
sphenopalatine foramen. In most cases, the tumor ex- 
pands the pterygopalatine fossa and extends into the 
sinonasal cavities, nasopharynx, orbital apex and cav- 
ernous sinus (Fig. 2). Common presenting symptoms in- 
clude recurrent spontaneous epistasis and nasal obstruc- 
tion; more advanced cases may show proptosis or cra- 
nial nerve deficits. The histologic makeup of angiofi- 
bromas consists of fibrous tissue with many thin-walled 
vessels that lack contractile tissue. Extensive biopsy is 
discouraged due to the strong vascularity of these tu- 
mors. Surgery is the treatment of choice, with preoper- 
ative embolization via the feeding arterial pedicles in 
order to reduce blood loss. MRI demonstrates a lesion 
with intermediate signal intensity on Tl- and T2- 
weighted images; multiple flow void channels are char- 
acteristic. There is typically prominent enhancement on 
both CT and Tl -weighted images following contrast 
medium infusion. CT shows a permeative type of bone 
erosion. Navigation CT may increase the likelihood of 
radical resection of tumors confined to the nasal cavity 
and paranasal sinuses. 

Chordoma 

Cranial chordomas arise near the spheno-occipital syn- 
chondrosis of the clivus and typically destroy the adjacent 
skull base. Large tumors show extensive bony inclusions 




Fig. 2. Angiofibroma of the pterygopalatine fossa with spread in- 
to the left orbital apex and cavernous sinus, a Top and b bottom 
T2-W image. There is marked expansion of the left pterygopala- 
tine fossa by a heterogenous tumor mass showing fine vascular 
flow voids, b The tumor is also seen in the orbital apex with a 
tongue of tissue extending along the lateral portion of the carotid 
artery in the cavernous sinus 



or calcifications within the soft tissue mass; the soft tis- 
sue component of chordomas is frequently dispropor- 
tionately large. So-called inferoclival chordomas may 
protrude anteriorly into the nasopharynx. The tumors 
may occur at any age but most affect men in the third and 
fourth decades. Chordomas are predominantly hy- 
pointense in signal on Tl -weighted images and charac- 
teristically show high signal intensity on T2-weighted im- 
ages. A heterogeneous pattern on MRI and CT is due to 
the presence of bone residue, calcification or hemor- 
rhage. Nearly all chordomas enhance vigorously and 
nonuniformly following the administration of contrast 
agents. 

Malignant Neoplasms of the Pharynx 

Malignant neoplasms of the nasopharynx represent 
0.25% of all malignancies in Caucasian patients. There is 
an incidence of 1 per 100 000 men and 0.4 per 100 000 
women. These neoplasms are much more common in pa- 
tients of southern Chinese origin, with an incidence of 1 8 
per 100 000. There is a strong indication of viral origin 
in a variety of malignant tumors of the nasopharynx. 




Imaging the Pharynx and Oral Cavity 



139 



Elevated titers of Epstein-Barr virus antibodies are found 
in almost all patients with advanced nasopharyngeal car- 
cinoma. 

Many patients with neoplasms of the nasopharynx pre- 
sent at the age of 40-50 years; however, these cancers can 
occur during infancy and childhood. The most common 
presenting symptoms include unilateral or bilateral con- 
ductive hearing loss, which is primarily due to obstruction 
of the eustachian tube with secondary serous otitis media. 
The second most common s 5 miptom is a cervical mass re- 
sulting from metastatic lymphadenopathy. Approximately 
one-third of patients presents with nasal obstruction, con- 
gestion, rhinorrhea or epistasis. Direct invasion by the tu- 
mor outside the nasopharynx may lead to cranial nerve 
deficits caused by involvement of the foramen ovale, cav- 
ernous sinus, petrous apex or jugular fossa. 

Neoplasms of the pharynx may be epithelial (e.g. un- 
differentiated carcinoma of nasopharyngeal origin, squa- 
mous cell carcinoma) or mesenchymal (e.g. lymphoma, 
lymphosarcoma, adenoid cystic carcinoma, adenocarci- 
noma) in origin or may derive from specialized tissues 
(e.g. rhabdomyosarcoma, malignant melanoma) [12-17]. 

Epithelial Malignant Carcinomas 

Epithelial malignant carcinomas represent 80% of all 
neoplasms of the nasopharynx. The remaining 20% com- 
prise a diverse group that includes tumors of mixed ep- 
ithelial origin such as lymphoepitheliomas and mucoep- 
itheliomas. The most common site of origin of these tu- 
mors is in the lateral recess of the nasopharynx. 

MRI is particularly superior to CT in this location. The 
tumor can spread directly exophytically into the airway 
and may extend inferiorly to invade the tonsillar pillars 
and soft palate. MRI depicts disruption of the musculo- 
fascial planes around the tensor and levator veli palatini 
muscles, skull base invasion and submucosal spread 
along the deep musculofascial planes or neural pathways. 
Anterior extension into the pterygoid muscles results in 
invasion of the nasal cavity and destruction of the ptery- 
goid plates; lateral spread involves the parapharyngeal 
spaces. Retropharyngeal lymph node involvement is 
common. Lesions greater than 5 mm in diameter are sus- 
picious, while those greater than 8 mm are highly proba- 
ble for metastatic involvement. The most effective treat- 
ment for epithelial nasopharyngeal carcinomas is radia- 
tion therapy, both with and without adjunct chemothera- 
py. Radiation therapy results in a 5-year survival rate of 
approximately 30%-50%. 

Lymphoma 

Malignant lymphoid neoplasms of the nasopharynx are 
usually non-Hodgkin’s lymphomas or lymphosarcomas 
[18]. They constitute approximately 18% of malignant 
neoplasms of the nasopharynx, the second-most com- 
mon site after the palatine tonsils. Patients typically pre- 
sent in the fourth through eighth decades. In young 



adults and children, there is a higher incidence of 
Hodgkin’s disease and Burkitt’s lymphoma. The Epstein- 
Barr virus is strongly associated with the development of 
lymphoproliferative disorders in post-transplant patients. 
In immunocompromised individuals, lymphoprolifera- 
tive disease should therefore be included in the differen- 
tial diagnosis. 

On MRI and CT, there are no specific distinguishing 
features that unmistakably point to the diagnosis of lym- 
phoma. However, a large mass that presents with little 
bony erosion points away from the diagnosis of squa- 
mous cell carcinoma. Lymphomas typically have inter- 
mediate signal intensity on the T1 -weighted images and 
relatively low, homogeneous signal intensity on T2- 
weighted images; they show moderate enhancement fol- 
lowing the administration of contrast medium. 
Lymphoid hyperplasia in Waldeyer’s ring also enhances, 
but there are internal septations. These fibrous septations 
help distinguish reactive hypertrophy from neoplasm. 
The treatment of choice for disseminated lymphoma is 
chemotherapy. 

Rhabdomyosarcoma 

Rhabdomyosarcomas of the head and neck are four- 
times more prevalent in Caucasian children than in chil- 
dren of other races. The disease is associated with a spe- 
cific chromosomal translocation in 50% of cases. The 
peak incidence is between 2 and 5 years of age, with 
70% of all cases observed in subjects less than 10 years 
of age [19]. Nearly one-third of head and neck rhab- 
domyosarcomas involve the pharynx. Most of these pha- 
ryngeal tumors affect the nasopharynx and are of the 
embryonal type. These tumors arise from the rhab- 
domyoblasts of the nasopharyngeal musculature. 
Invasion of the eustachian tube orifice and skull base is 
common and may result in serous otitis media and dys- 
function of the cavernous sinus cranial nerves. Large tu- 
mors tend to involve the nasal cavity, paranasal sinuses, 
or orbits. Bulky naso-oropharyngeal masses present 
with nighttime dyspnea. 

Imaging findings in rhabdomyosarcomas are similar to 
those of malignant epithelial carcinomas; however, since 
these neoplasms arise from muscle, they may not neces- 
sarily involve the mucosal space. The most typical find- 
ing is a bulky nasopharyngeal mass with signal intensity 
intermediate between those of muscle and fat on Tl- 
weighted images. Necrotic areas may be seen producing 
heterogeneous signal intensities on both Tl- and T2- 
weighted images. Following administration of contrast 
medium, there is variable, heterogeneous enhancement of 
both the primary neoplasm and any associated metastat- 
ic lymph nodes. 

Malignant Melanoma 

Primary nasopharyngeal melanomas are rare, accounting 
for less than 1% of all malignant melanomas [20]. More 




140 



B. Schuknecht, A.N. Hasso 



often, there may be metastasis to the nasopharynx from a 
primary tumor elsewhere. There are racial differences, 
with a higher incidence of mucosal melanomas in persons 
of Japanese origin. The melanocytes in the nasal cavity are 
located primarily in the nasal septum or in the turbinates. 
Such tumors enlarge to involve the nasopharynx by direct 
extension. With MRJ, it is possible to determine the extent 
of tumor. Melanomas have relatively homogeneous signal 
intensity, unless there is evidence of associated hemor- 
rhage. Non-hemorrhagic lesions tend to be hypointense or 
isointense on T1 -weighted images and isointense or hy- 
perintense on T2-weighted images. Melanomas generally 
show moderate enhancement following administration of 
contrast media. Post-contrast T1 -weighted fat-suppressed 
scans are useful in the search for evidence of parapharyn- 
geal, skull base and intracranial involvement. 

Squamous Cell Carcinoma of the Oropharynx 

Oropharyngeal squamous cell carcinomas, including the 
lymphoepithelioma variant, are usually poorly differenti- 
ated. These tumors are characterized by extensive prima- 
ry disease with a 50%-70% incidence of cervical lymph 
node metastasis (Table 1) and a 10%-20% incidence of 
bilateral lymph node disease if the midline structures are 
affected. Early disease is rarely recognized since patients 
usually are asymptomatic. Some early lesions may be de- 
tected on discovery of a neck mass. Persistent unilateral 
sore throat, referred otalgia and difficulty in speech or 
swallowing are symptoms of advanced disease. 
Squamous cell carcinomas of the oropharynx have a 
propensity to spread extensively along the mucosal sur- 
faces of the soft palate, lateral pharyngeal wall and base 
of the tongue. The three sites of squamous cell carcino- 
ma of the oropharynx are the tonsils, base of the tongue, 
and oropharyngeal wall. 

Carcinoma of the tonsil is prone to spread posteriorly 
to the lateral pharyngeal wall, inferiorly to the base of the 
tongue, and superiorly to the soft palate. This tumor can 
also grow directly into the soft tissues of the neck and 
posteriorly and laterally to invade the carotid artery. 
Lymph node metastasis is present in 60%-70% of pa- 



Table 1. Incidence and location of cervical lymph node metastases 
aecording to the site of the primary tumor 



Site of primary 
tumor 


Incidence of lymph 
node metastasis, % 


Nodal levels 
involved 


Nasopharynx 


86-90 


II, III, IV 


Tongue (base) 


50-83 


II, III, IV 


Tonsillar fossa 


58-76 


I, II, III, IV 


Hypopharynx 


52-75 


II, III, IV 


Oropharynx 


50-71 


II, III 


Tongue (oral portion) 


34-65 


I, II, III 


Floor of mouth 


30-59 


I, II 


Retromolar trigone 


39-56 


I, II, III 


Soft palate 


37-56 


II 


Supraglottic larynx 


31-54 


II, III, IV 



tients. Bilateral nodal involvement is seen in 1 5%-20% of 
cases in which a large portion of the base of the tongue 
or soft palate is involved by carcinoma. 

Squamous cell carcinomas of the base of the tongue 
are aggressive, deeply infiltrative, moderately or poorly 
differentiated neoplasms. There is a 75% incidence of 
lymph node metastasis at presentation (33%-50% of 
which are bilateral) due to a rich lymphatic network. 
The most commonly involved lymph nodes are the jugu- 
lodigastric, jugulo-omohyoid and the more cephalad 
lymph nodes of the internal jugular chain. Of all clini- 
cally normal lymph nodes, 10%-20% has occult 
metastatic disease. 

Early disease is rarely detectable since the patient is 
often asymptomatic. Moderately advanced tumor pre- 
sents with pain, unilateral sore throat, odynophagia, dys- 
phagia, otalgia and occasionally hemorrhage. Early dis- 
ease is radiosensitive and curable by radiation alone (with 
results comparable to those of surgery without mutila- 
tion), while late disease requires combined radiation and 
surgical treatment or chemotherapy. 

Sagittal and coronal MR images permit an excellent 
appreciation of the volume of tumor in the tongue base. 
Such carcinomas are usually hyperintense on T2 -weight- 
ed images, may form ulcerative bulky masses, or may 
present as deeply infiltrative processes along the muscle 
planes. Carcinoma of the base of the tongue is distin- 
guished from tonsillar hyperplasia by the invasion and 
disruption of the muscle bundles of the tongue. Following 
the administration of gadolinium chelates, there is t 5 q)i- 
cally fairly intense enhancement. 

The lateral and posterior portions of the oropharynx 
and the posterior tonsillar pillar form the oropharyngeal 
wall. Squamous cell carcinomas of this region are often 
ulcerative and may infiltrate inferiorly into the hypophar- 
ynx. Such tumors are usually moderately or poorly dif- 
ferentiated. Because of the lack of early symptoms, 75% 
of patients present with extensive primary disease and 
lymph node metastasis, frequently bilaterally. The most 
commonly involved lymph nodes are the jugulodigastric 
and jugulo-omohyoid nodes of the internal jugular chain 
and the lateral retropharyngeal lymph nodes. 

Squamous Cell Carcinoma of the Hypopharynx 

Squamous cell carcinomas of the hypopharynx are pre- 
dominantly moderately or poorly differentiated tumors. 
These neoplasms spread with ease from one anatomic 
site to another as well as from the hypopharynx to the lar- 
ynx, since there are no fascial boundaries between these 
structures. Common sites are the piriform sinus (65%), 
followed by the post-cricoid area (20%) and the posteri- 
or pharyngeal wall (15%). The incidence of lymph node 
metastasis is 50%-70%, with 10%-20% bilateral involve- 
ment owing to the rich lymphatic pathways in the hy- 
popharynx. 

Early symptoms of hypopharyngeal carcinomas in- 
clude sore throat, intolerance to hot and cold liquids, dys- 




Imaging the Pharynx and Oral Cavity 



141 



phagia, odynophagia and ipsilateral otalgia. Whenever 
otalgia is present, the tumor is large and has invaded the 
superior laryngeal nerve with referred pain via the throat 
back to the vagus nerve. Involvement of the post-cricoid 
area leads to dysphagia, while extensive carcinomas of 
the piriform sinus result in hoarseness, laryngeal stridor 
and hemoptysis. 

Piriform sinus carcinomas are usually unilateral and 
submucosal in location. Deep extension of the disease 
and lymph node metastasis are well evaluated with CT 
and MRI. T1 -weighted images maximize contrast be- 
tween the intermediate signal of the tumor and the bright 
signal in adjacent loose areolar tissue. Tumors originat- 
ing from the apex of the piriform sinus are aggressive 
and infiltrative with extension into the adjacent posteri- 
or margin of the thyroid cartilage and infrahyoid mus- 
cles. Spread of disease towards the larynx and trachea is 
common. 

Carcinoma of the post-cricoid area is usually well 
differentiated and thought to represent an “iceberg” 
presentation of carcinoma of the upper cervical esoph- 
agus, especially involving the anterior wall of the 
esophagus. Despite aggressive surgery, the 5-year sur- 
vival is 10%-20% owing to extensive spread of disease 
at the time of initial presentation. This site has the 
worst prognosis of all three sites of carcinoma of the 
hypopharynx. 

Carcinoma of the posterior pharyngeal wall is the least 
common carcinoma of the hypopharynx. Such lesions are 
large and exophytic at presentation, and may extend to 
the lateral pharyngeal wall or to the cervical esophagus 
below. The prevertebral muscles and the vertebral bodies 
may not be involved until late in the disease, owing to the 
presence of the prevertebral fascia. About 50% of afflict- 
ed patients have cervical lymph node metastasis at diag- 
nosis, often bilaterally. 

Imaging the Oral Cavity 

Anatomy 

The oral cavity [14, 15, 21] includes the floor of the 
mouth, the anterior two-thirds of the tongue, lips, and 
gingivobuccal (oral vestibule) and buccomasseteric re- 
gions. The oral cavity is separated from the oropharynx 
by the circumvallate papillae of the tongue, the soft palate 
and palatoglossal arch (anterior tonsillar pillar). The pos- 
terior one-third of the tongue belongs to the oropharynx. 

The tongue is composed of the intrinsic musculature 
(superior and inferior longitudinal, transverse and verti- 
cal muscle fibers) and extrinsic muscles (genioglossus, 
styloglossus, hyoglossus and palatoglossus), which orig- 
inate externally to the tongue but insert into the tongue 
itself 

The floor of the mouth is composed of the mylohyoid 
muscles united by a median raphe and the midline ge- 
niohyoid muscles located below the genioglossus mus- 



cles, and is supported inferiorly by the anterior belly of 
the digastric muscles. These muscles border the trian- 
gular submental space that contains fat and lymph nodes 
(nodal level lA). At the posterior margin of the mylohy- 
oid muscles, the submandibular gland extends through 
a gap between the hyoglossus and mylohyoid muscles. 
Its deep portion is contained in the sublingual space to- 
gether with the sublingual gland, the submandibular 
duct (Wharton’s duct), the hypoglossal and lingual 
nerves laterally and the lingual artery and vein medial- 
ly. Posteriorly the sublingual space communicates with 
the submandibular space. The submandibular space 
contains lymph nodes (level IB) and the submandibular 
gland, with the facial artery medially and the facial vein 
laterally. 

The oral vestibule separates the lips and cheeks from 
the teeth and alveolar process by a reflection of buccal 
mucosa onto the maxilla and mandible. Adjacent to the 
alveolar process, the gingivobuccal sulcus and the glos- 
so-alveolar sulcus are common locations for squamous 
cell carcinoma of the vestibule and floor of the mouth, 
respectively. The retromolar trigone between the third 
molar and the ramus mandibulae is another frequent 
site. The pterygomandibular raphe is a fascial band ex- 
tending from the hamulus to the mylohyoid ridge of the 
mandible and thus provides origin for the buccinator 
and superior pharyngeal constrictor muscles. 
Retromolar malignancies may spread along this path- 
way to the tuber maxillae superiorly and to the 
retroantral masticator space posteriorly and inferiorly 
to reach the floor of the mouth. The buccomasseteric 
region is composed of the buccal space traversed by the 
parotid duct, the buccinator and masseter muscles and 
the body of the mandible. 

Benign Lesions of the Oral Cavity 

Germ Cell Derivatives 

Germ layer derivatives embedded during midline closure 
of the first and second branchial arches lead to formation 
of developmental lesions that are termed either teratomas 
or dermoid cysts. These terms are commonly used syn- 
onyms that refer to all three types of manifestations: epi- 
dermoid, dermoid and teratoid cysts. 

Epidermoid cysts (ectodermally derived) are com- 
posed of squamous epithelium contained within a fibrous 
wall. Dermoids (ectodermal and mesodermal compo- 
nents) additionally contain hair follicles, sebaceous 
glands and fatty tissue. Teratoid cysts are composed of 
any kind of ecto-, meso- or entodermal tissue and bear 
the name teratoma if recognizable organs are found. 
Dermoids are commonly found along the floor of the 
mouth (and within the orbit and median nose). 
Depending on the amount of fatty tissue, they appear less 
dense on CT and T1 -hyperintense compared to epider- 
moids; the T2 signal is hyperintense in both manifesta- 
tions. The cyst wall displays mild enhancement. Contrary 




142 



B. Schuknecht, A.N. Hasso 



to epidermoids, dermoid and teratoid cysts bear malig- 
nant potential. However, teratoid cysts in the floor of the 
mouth or nasopharynx are usually composed of well-dif- 
ferentiated tissues. 

Vascular Lesions 

In infancy and childhood, two types of vascular lesions 
are encountered: hemangiomas and vascular malforma- 
tions. 

Hemangiomas are tumors characterized by endothe- 
lial cell proliferation and formation of vascular channels 
within a soft tissue stroma. They commonly become ap- 
parent within the first months of life, enlarge rapidly 
during a proliferative phase and subsequently regress by 
adolescence. Bluish discoloration of the skin and com- 
pressibility are encountered as well as subcutaneous and 
deep locations that affect the pharynx, oral cavity, glan- 
dular tissue, or orbits. Hemangiomas require abstention 
from treatment unless functional compromise (respira- 
tion, deglutition, vision) occurs. Hemangiomas are typ- 
ically hyperintense on T2-weighted MR images, en- 
hance moderately, and may contain flow voids in the 
proliferative stage, indicating the early high-flow nature 
of the lesion. 

Vascular malformations, unlike hemangiomas, are 
not tumors but inborn errors of vascular morphogene- 
sis. Based on the predominant type of the vascular 
component, angiomas or vascular malformations are 
classified into capillary, arterial, venous and lymphatic 
malformations. Vascular malformations are present 
since birth and grow commensurate with the growth of 
the child, even though endocrine stimuli or trauma in- 
cluding surgery may cause exacerbation. Capillary 
malformations (port-wine stain, nevus flammeus) are 
slow-flow lesions that occur in an isolated fashion or as 
part of several syndromes (e.g. Sturge- Weber, ataxia- 
telangiectasia, Rendu-Osler- Weber, Wyburn-Mason’s, 
Cobb’s). Venous malformations commonly affect the 
oral cavity or may be entirely intramuscular, most com- 
monly within the masseter muscle. T2 hyperintensity, 
gadolinium enhancement on MRI, muscle isodensity 
on CT and rounded phleboliths are characteristic find- 
ings. Arteriovenous malformations are high-flow le- 
sions that may attain large size with abundant flow 
voids affecting the midface, masticator space and oral 
cavity. Lymphatic malformations or lymphangiomas 
display increased signal on T1 -weighted images and 
mild hyperdensity due to high protein content. 
Lymphangiomas represent a continuum of lesions that 
includes cystic hygromas, cavernous and capillary lym- 
phangiomas, and lymphangiomas with additional vas- 
cular elements (hemangiolymphangiomas). Any of 
these components may be found in a single lesion. 
Fluid-fluid levels due to hemorrhage may occur. 
Hemangiomas and lymphangiomas are ill-defined le- 
sions, unlike the cystic hygroma that is preferentially 
located in the posterior triangle of the neck and within 



the sublingual and submandibular spaces. The cav- 
ernous type commonly affects the floor of the mouth, 
tongue or salivary glands in a permeative pattern, but 
presents with less contrast enhancement than a deeply 
located hemangioma. 

Benign Cystic Lesions 

Ranulas are mucous retention cysts due to obstruction of 
a gland, most commonly the sublingual gland. Simple 
ranulas are true cysts, while the plunging ranula develops 
following rupture of the cyst wall (pseudocyst) and pre- 
sents as a lesion extending posteriorly into the sub- 
mandibular space. A “cystic” lesion in relationship to the 
submandibular gland thus may be a ranula (medial), a 
second branchial cleft cyst (posteriorly), a dermoid, cys- 
tic hygroma, or lipoma (commonly anteriorly). An ex- 
travasation mucocele is a pseudocystic lesion in the ante- 
rior submandibular space following obstruction and dis- 
ruption of the submandibular duct caused by trauma, tu- 
mor or sialolithiasis. 

The thyroglossal duct cyst is the most common con- 
genital lesion located in the midline between the foramen 
cecum and the level of the hyoid. Infrahyoid cysts (50%- 
65%) frequently extend off midline encased within the 
infrahyoid muscles along the course of the embryonic 
thyroglossal duct. Persistent thyroid tissue may occur 
anywhere along the duct and typically enhances marked- 
ly on CT and MRI studies. The possibility of malignan- 
cy (usually papillary carcinoma) or infection should be 
taken into consideration. 

Inflammatory and Infectious Lesions 

Inflammation of the floor of the mouth, the submental or 
submandibular space, and the buccomasseteric region 
may arise from ductal obstruction due to sialolithiasis, 
strictures or a neoplasm obliterating the orifice of 
Wharton’s (submandibular) duct or Stensen’s (parotid) 
duct. Glandular inflammation {sialadenitis) may display 
swelling and increased contrast medium uptake by the 
gland and its fascial lining. CT is superior to convention- 
al radiography to depict sialolithiasis in glandular in- 
flammation. This holds true despite advanced techniques 
like MR sialography. Frank parenchymal abscess forma- 
tion is rare and in the absence of a predisposing condition 
should imply a search for a specific (tuberculous) etiolo- 
gy. Inflammation within the oral cavity may alternatively 
arise from infection of a preexisting lesion (ranula, der- 
moid, thyroglossal duct cyst) or may be of odontogenic 
origin. 

Periapical or periodontal disease that gains access to 
the subperiosteal space may eventually lead to peri- 
mandibular phlegmonous infiltration or abscess forma- 
tion. Access to cancellous bone and cortical bone via 
Volkmann’s canals results in mandibular osteomyelitis 
[23]. An orthopantomogram supplemented by CT with 
bone window algorithm is the imaging modality of 




Imaging the Pharynx and Oral Cavity 



143 



choice to recognize complications of odontogenic infec- 
tion. Early signs are cortical bone erosion and periosteal 
reactions; later signs include sequestration, pathologic 
fracture and progressive bone sclerosis. MRI, however, is 
superior to CT in recognition of bone marrow involve- 
ment in osteomyelitis or the unusual development of in- 
tramuscular or subperiosteal masticator space abscess de- 
rived from dentogenic infection. 

Benign Tumors 

In the oral cavity and buccal space [24], pleomorphic 
adenomas are the most common benign glandular tu- 
mors. Lesions may cause pressure erosion at the posteri- 
or hard palate, and display cystic changes, hypodensity 
with little enhancement on CT, and T2 hyperintensity 
and inhomogeneous enhancement on MRI. Malignant 
minor salivary gland tumors in the oral cavity and buc- 
cal space usually are also well defined [24]. A similar 
imaging appearance is found in schwannomas. The 
tongue, floor of the mouth and hard palate are the most 
common locations in the oral cavity. Oral neurofibromas 
as a manifestation of von Recklinghausen’s syndrome 
are rare (4%-5%). Rhabdomyomas are benign, frequent- 
ly encapsulated tumors of striated muscle that occur in 
middle-aged men and preferentially affect the base of the 
tongue, floor of the mouth and pharynx. Granular cell 
myoblastomas contain neurogenic and muscular ele- 
ments and most probably are of primitive neuroectoder- 
mal origin. As nonencapsulated tumors, they may dis- 
play a more infiltrating pattern. The lesions are of mus- 
cle density and signal intensity. Overall, 50% affect the 
oral cavity, the dorsum and lateral tip of the tongue in 
particular. 

Malignant Neoplasms of the Oral Cavity 

Overall, 90% of malignancies of the oral cavity con- 
sist of squamous cell carcinoma (SCC). Other neo- 
plasms are minor salivary gland tumors (e.g. adeno- 
cystic carcinoma, adenocarcinoma, mucoepidermoid 
carcinoma), sarcomas, and lymphomas. The squamous 
epithelium within the oral cavity originates from ecto- 
derm and thus gives rise to better-differentiated neo- 
plasms than the entodermally derived mucosa of the 
oropharynx. 

The questions answered by imaging [14, 15, 21] relate 
to precise description of the tumor location, submucosal 
and potential neurovascular spread, and cortical bone 
and lymph node involvement. Common sites for SCC are 
the floor of the mouth, tonsillar pillar, retromolar trigone 
and lateral tongue, in decreasing order of frequency. 
SCC of the floor of the mouth is most commonly found 
in the anterior third and may spread medially to obstruct 
the submandibular duct, laterally and posteriorly within 
the glosso-alveolar sulcus along the mylohyoid muscle 
to affect the lingual and occlussal cortical mandibular 
surfaces, and along the neurovascular bundle within the 



sublingual space. Small tumors may be missed on axial 
sections both by CT or MRI, unless the coronal images 
are scrutinized. Lymph node drainage affects the sub- 
mental (nodal level lA), submandibular (IB) and jugu- 
lodigastric (II) lymph nodes. SCCs of the lateral tongue 
originate from the middle and posterior thirds and tend 
to invade the intrinsic and extrinsic tongue muscles. 
Assessment of midline involvement is important as is 
recognition of extension to the floor of the mouth and to 
the soft palate via the anterior tonsillar pillar. 
Carcinomas of the gingiva, the gingivobuccal sulcus and 
retromolar trigone are prone to cause mandibular ero- 
sion, and spread into the buccal space and masticator 
space [25]. 

Anterior tonsillar pillar carcinomas may mimic a tu- 
mor arising in the retromolar trigone due to extension 
along the palatoglossus muscle and the pterygomandibu- 
lar raphe. However, invasion of the tongue base in more 
advanced tonsillar tumors and superior extension into the 
soft palate and ipsilateral nasopharynx are distinguishing 
features. Levels I and II lymph nodes are primarily af- 
fected. MRI in most instances excludes dental artifacts 
and is superior to CT in recognition of the pathways of 
extension. Early recognition of cortical bone erosion, 
however, requires high-resolution CT. Obliteration of fat 
by tumor extension along the nasopalatine nerves into the 
pterygopalatine fossa and widening of the descending 
palatine canal are signs indicating perineural tumor 
spread or recurrence, and have important therapeutic im- 
plications. 

Staging of Cancer of the Pharynx and Oral 
Cavity 

Accurate staging [26, 27] is the most important factor in 
assessment, treatment planning, and prognosis in patients 
with head and neck cancer. The staging system of the 
American Joint Cancer Committee (AJCC) incorporates 
three aspects of tumor growth: the extent of primary tu- 
mor (T), the involvement of regional lymph nodes (N), 
and distant metastasis (M). 

The primary tumor (T) is scored as follows: 

TX Primary tumor cannot be assessed 
TO No evidence of primary tumor 
Tis Carcinoma in situ 

T1-T4 Increasing size or local extent of the primary tu- 
mor 

The exact definitions of T1-T4 depend on the actual 
site of the primary tumor (Table 2). T4 lesions are further 
subdivided into: T4A (resectable), T4B (unresectable), 
and T4C (advanced distant metastasis). 

Nodal involvement (N) is scored with the following 
system: 

NX Regional lymph nodes cannot be assessed 
NO No regional lymph node metastasis 
N1 Metastasis in single ipsilateral lymph node, 3 cm 
or less in greatest dimension 




144 



B. Schuknecht, A.N. Hasso 



N2a Metastasis in single ipsilateral lymph node, more 
than 3 cm but not more than 6 cm in greatest di- 
mension 

N2b Metastasis in multiple ipsilateral lymph nodes, 
none more than 6 cm in greatest dimension 
N2c Bilateral or contralateral metastatic lymph nodes, 
none more than 6 cm in greatest dimension 
N3 Metastasis in a lymph node, more than 6 cm in 
greatest dimension 

Finally, distant metastases (M) are scored as follows: 
Mx Distant metastasis cannot be assessed 
MO No known distant metastasis 
Ml Distant metastasis present (specify area or struc- 
ture) 

The resulting tumor stages are then defined by the 
combination of tumor (T), node (N) and metastasis (M) 



scores: 



Stage I 


TI 


NO 


MO 


Stage II 


T2 


NO 


MO 


Stage III 


T3 


NO 


MO 




TI orT2orT3 


NI 


MO 


Stage IV 


T4 


NO or NI 


MO 




Any T 


N2 or N3 


MO 




Any T 


Any N 


Ml 



Table 2. Definitions of T1-T4 for tumors of the pharynx and oral 
cavity [27] 



Primary tumor 


Definition 


Nasopharynx 


TI 


Tumor confined to one site of nasopharynx or no 
tumor visible (positive biopsy only) 


T2 


Tumor involving two sites (both posterosuperior 
and lateral walls) 


T3 


Extension of tumor into nasal cavity or oropharynx 


T4 


Tumor invasion of skull base or cranial nerve in- 
volvement, or both 


Oropharynx and oral cavity 


TI 


Tumor 2 cm or less in greatest diameter 


T2 


Tumor more than 2 cm but not more than 4 cm in 
greatest diameter 


T3 


Tumor more than 4 cm in greatest diameter 


T4 


Massive tumor more than 4 cm in diameter with in- 
vasion of contiguous structures 


Hypopharynx 


TI 


Tumor confined to site of origin 


T2 


Extension of tumor to adjacent region or site with- 
out fixation of hemilarynx 


T3 


Extension of tumor to adjacent region or site with 
fixation of hemilarynx 


T4 


Massive tumor invading bone or soft tissues of the 
neck 



Imaging Cervical Metastasis 

Imaging is especially useful in patient management 
whenever metastatic nodes are found in a clinically neg- 
ative neck. The main imaging criteria for assessing nodal 
metastases [28-30] include the size and shape of the 
node, the presence of necrosis, and the presence of a lo- 
calized group of nodes in an expected nodal draining area 
for a specific primary tumor (Table 1). 

There is disagreement about the best way to measure 
nodes, but in the simplest case, nodes are considered ab- 
normal if they are larger than 10 mm in diameter. 
Exceptions include the larger level II nodes and the 
smaller retropharyngeal nodes that are considered abnor- 
mal if their diameters exceed 15 mm and 8 mm, respec- 
tively. Imaging cannot yet identify microscopic tumor fo- 
ci. Normal lymph nodes are oval or oblong, while 
metastatic lymph nodes are round or spherical. 

Central nodal necrosis is considered a more specific 
sign of metastasis. Evaluation sensitivity is enhanced sig- 
nificantly when both necrosis and nodal size are used as 
criteria. On CT, necrosis appears as a rim of irregular en- 
hancement surrounding a hypoattenuated central region. 
On post-contrast, fat-suppressed, T1 -weighted MR im- 
ages, peripheral enhancement surrounds a central hy- 
pointense area. Infection, prior surgery and irradiation 
can produce similar findings. 

Extranodal tumor spread decreases survival by 50% 
compared to confined tumors. Extranodal extension is seen 
on CT and MR images as a poorly defined nodal border 
with variable enhancement. In addition, there may be oblit- 
erated fat planes adjacent to the node. Any lymph node 
with ill-defined margins is abnormal. The combination of 
nodal capsular penetration and the presence of a nodal 
mass surrounding at least 75% of an adjacent structure is 
highly suggestive of fixation to the adjacent structure. 

The most common malignant neoplasm of the ex- 
tracranial head and neck in patients older than 40 years is 
metastatic disease. In approximately 5% of cancer patients 
and nearly 15% of head and neck cancer patients, the sole 
presenting sign is cervical metastasis. Metastasis to the 
neck soft tissues can take other forms such as direct ex- 
tension of a neoplasm or perineural spread of tumor. 

The primary neoplasms that commonly metastasize to 
the cervical lymph nodes are the squamous cell carcino- 
mas of the head, neck, esophagus and lung. Metastasis to 
the neck can also occur by direct extension of a primary 
or metastatic bone tumor of the mandible or spine. 
Finally, distal perineural spread may occur along the cra- 
nial and spinal nerves, thus gaining access to noncon- 
tiguous regions of the neck. 

References 

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Imaging the Pharynx and Oral Cavity 



145 



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head and neck tumors. WB Saunders, Philadelphia, p 778 

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pp 1828-1864 

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mandible. Neuroimaging Clin N Am 13:605-618 

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Berlin Heidelberg New York, pp 133-156 




IDKD 2004 



Imaging of the Larynx 

H.D. Curtin 

Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA 



Introduction 

Imaging of the larynx must be coordinated with the clin- 
ical exam. The information acquired at imaging usually 
emphasizes the deeper tissues, as the superficial assess- 
ment is done by direct visualization. The description of 
anatomy is key to the description of any lesion. 

Anatomy 

Important Mucosal Landmarks 

Several key anatomic structures are important to the ra- 
diologist seeking to evaluate the larynx. Perhaps the most 
important relationship in the larynx is that of the false vo- 
cal folds, true vocal folds and ventricle complex. The 
ventricle is a crucial reference point. Much imaging of tu- 
mors is aimed at defining the position of a lesion relative 
to this key region. Another important landmark is the 
cricoid cartilage. This cartilage is the only complete ring 
of the cartilage framework and is key to the integrity of 
the airway. 

A major role in speech generation is played by the glot- 
tis or true vocal folds (cords). They stretch across the low- 
er larynx and are in the horizontal or axial plane. There is 
a small crease just above the true vocal folds called the 
ventricle. Immediately above the ventricle and again par- 
allel to both the ventricle and true folds is a second pair 
of folds called the false vocal folds. Above the false folds, 
the mucosa curves out laterally to the upper edges of the 
larynx called the aryepiglottic folds which, in turn, curve 
around and extend up to the margins of the epiglottis. 

These structures are the basis for anatomic localization 
within the larynx. The glottic larynx refers only to the 
true folds. It has been defined as stretching from the ven- 
tricle to a plane approximately one centimeter below the 
ventricle. Here, the glottis merges with the subglottis (the 
lower part of the larynx). The subglottis extends from the 
lower margin of the glottis to the inferior margin of the 
cricoid cartilage. Everything above the ventricle of the 
larynx is the supraglottis. 



Another important anatomic term relating to the mu- 
cosa is the anterior commissure. This is the point where 
the true folds converge anteriorly and insert into the thy- 
roid cartilage. 

Cartilage Framework 

The cartilages make up the framework of the larynx and 
give it structure. The cricoid cartilage is the foundation 
of the larynx and is the only complete ring. It is re- 
sponsible for keeping the airway open. Above the 
cricoid cartilage and attached its lateral margins is the 
thyroid cartilage. This shield-like cartilage provides 
protection to the inner workings of the larynx. The ary- 
tenoid cartilages perch upon the posterior edge of the 
cricoid cartilage. 

In axial imaging, the cartilages can help orient us to 
the mucosal levels in the larynx. The cricoid is at the lev- 
el of the glottis and subglottis. The upper posterior edge 
of the cricoid cartilage is actually at the level of the true 
folds. The lower edge of the cricoid cartilage represents 
the lower boundary of the larynx and, therefore, the low- 
er edge of the subglottis. 

The arytenoid cartilage spans the ventricle. The upper 
arytenoid is at the level of the false folds, whereas the vo- 
cal process defines the position of the vocal ligament and, 
therefore, the true folds. The epiglottis is totally within 
the supraglottic larynx. 

Deep Soft Tissues 

There are many muscles within the larynx. The key mus- 
cle for the radiologist is the thyroarytenoid muscle. This 
forms the bulk of the true folds and extends from the ary- 
tenoid up to the anterior part of the thyroid cartilage at 
the anterior commissure. The radiologist should be fa- 
miliar with this muscle because identifying it is helpful 
in attempting to identify the true folds. 

The paraglottic space refers to the major part of the 
soft tissue between the mucosa and the cartilaginous 
framework of the larynx. At the supraglottic or false fold 
level, this is predominantly made up of fat, whereas at the 




Imaging of the Larynx 



147 



level of the true folds, the paraglottic region is filled with 
the thyroarytenoid muscle. Again, this concept is helpful 
in orienting oneself to the level within the larynx. The 
level of the ventricle is identified as the transition be- 
tween the fat and muscle. 



Pathology and Imaging 

Imaging of the larynx and upper airway is done in many 
situations [1-6]. At Massachusetts Eye and Ear Infirmary, 
most laryngeal imaging studies relate to the evaluation of 
tumor or trauma. 

Tumors of the larynx can be separated into two cate- 
gories. Most tumors of the larynx are squamous cell car- 
cinomas and arise from the mucosa. A few tumors arise 
from the cartilaginous skeleton or from the other submu- 
cosal tissues. 

The endoscopist almost always detects and diagnoses 
the mucosal lesions. Indeed, imaging should not be used 
in an attempt to "exclude” squamous cell carcinoma of 
the larynx. In squamous cell carcinoma, the role of the 
radiologist is almost always to determine the of depth of 
spread. Submucosal tumors are, however, somewhat dif- 
ferent. These the endoscopist can usually visualize, but 
since they are covered by mucosa there may be consid- 
erable difficulty in making the diagnosis; in these cases 
the clinician may ask the radiologist to identify the type 
of tumor. 

In squamous cell carcinoma, much of imaging con- 
cerns the determination of the depth of extension. 
Radiologists can see submucosal disease, which can 
make a difference in choice of therapy. It is important to 
know some of the indications and contraindications of 
various alternatives to total laryngectomy. Standard clas- 
sic partial laryngectomies are supraglottic laryngectomy 
and vertical hemilaryngectomy. In many institutions, sim- 
ilar surgeries are now done via endoscopic approach. If 
the information needed for these procedures is gathered 
through imaging, then there is more than enough infor- 
mation for radiotherapists and other clinical specialists as 
well. 

- Supraglottic laryngectomy removes everything above 
the level of the ventricle, and is used for tumors aris- 
ing in the epiglottis, false folds or aryepiglottic folds. 
Tumor may obstruct the endoscopist's view of the low- 
er margin of the tumor, or can cross the ventricle by 
"tunneling" beneath the mucosal surface. Such sub- 
mucosal spread can travel along the paraglottic path- 
way around the ventricle, and is a contraindication to 
supraglottic laryngectomy. Since it can be missed by 
direct visualization, the radiologist must try to detect 
this phenomenon. Cartilage involvement is another 
contraindication, but this is rare in supraglottic cancers 
unless the lesion has actually crossed the ventricle. 
Other contraindications include significant extension 
into the tongue or significant pulmonary problems. 
These mostly relate to difficulty in relearning how to 



swallow once the key part of the laryngeal protective 
mechanism has been removed. 

- Vertical hemilaryngectomy is performed for lesions of 
the true folds. The aim is to remove the tumor but to re- 
tain enough of one true fold so that the patient can still 
create speech using the usual mechanism. Actually, the 
lesion can extend onto the anterior part of the opposite 
fold and there can still be a satisfactory removal. In 
these areas, the radiologist looks most closely at inferi- 
or extension. Does the tumor reach the upper margin of 
the cricoid cartilage? In most institutions, such exten- 
sion would mean that the patient is not a candidate for 
vertical hemilaryngectomy but rather should have total 
laryngectomy or alternative therapies. 

Lesions of the anterior commissure may extend ante- 
riorly into either the thyroid cartilage or through the 
cricothyroid membrane into the soft tissues of the neck. 
This may be invisible to the examining clinician and is 
again a key point to evaluate. 

Involvement of both the arytenoid cartilages is also a 
contraindication to total laryngectomy, but this is usually 
evaluated by direct visualization. 

Radiotherapy is a speech-conserving treatment. Here 
the therapist is mostly concerned with cartilage invasion 
or the thickness of the tumor. 

In order to image laryngeal squamous cell carcinoma, 
at Massachusetts Eye and Ear Infirmary, we begin with 
computed tomography (CT). The new multidetector CT 
scanners give excellent resolution and good coronal and 
sagittal plane image reformats. The study can be done in 
a short time interval. Newer scanners can perform the en- 
tire study during a single breath hold. Magnetic reso- 
nance imaging (MRI) is reserved for evaluating lesions 
close to the cartilage or ventricle. A limited study may be 
done to clarify a particular margin. 

Imaging of cartilage involvement is controversial. 
Some clinicians favor CT while others prefer MRI. At 
CT, sclerosis of the cartilage and obliteration of the low 
density fat in the medullary space indicate involvement. 
The negative finding, intact fat in the medullary space 
with a normal cortex, is considered reliable. On MRI, 
one begins with the T1 -weighted image. If there is high 
signal intensity in the medullary space, the cartilage is 
considered normal. If the area is dark, then one examines 
the T2-weighted image. Nonossified cartilage remains 
dark while tumor is usually brighter. High signal inten- 
sity on T2-weighted images can mean tumor or edema 
related to tumor; at my institution, the high signal inten- 
sity is presumed to represent tumor. More research is 
needed to determine the relevance of signal changes to 
prognosis. 

Submucosal lesions may arise from the cartilages, mi- 
nor salivary glands, or other soft tissue structures. CT with 
intravenous contrast medium administration can be help- 
ful. Chondromatous lesions can arise from any cartilage. 
Those arising from the cricoid cartilage have a character- 
istic appearance as they expand cartilage. Hemangiomas 
enhance intensely as do the rare glomus (paraganglioma) 




148 



H.D. Curtin 



tumors. There are other lesions that arise in the submu- 
cosal region but do not enhance nor involve the cartilage. 
In these cases, the identity cannot be made precisely but 
it is helpful to the clinician if one can exclude a vascular 
or chondroid lesion. 

Another submucosal lesion that is important is the 
laryngocele. This lesion can present as a submucosal 
swelling but is actually totally benign and results from 
obstructive dilatation of the small saccule (appendix) of 
the ventricle. Although benign, it may be associated with 
a malignancy at the level of the ventricle. It is important 
to carefully evaluate this level. Again, we must realize 
that radiologically we cannot totally exclude small le- 
sions of the mucosa. This must be done endoscopically. 

Trauma 

Trauma to the airway can obviously be life-threatening. 
Most patients who have a demonstrable fracture of the 
larynx undergo endoscopy to identify mucosal tears. If 
there is a fragment of cartilage exposed to the airway, 
then chondritis and eventual chondronecrosis can be ex- 
pected. One should carefully evaluate the integrity of the 
thyroid cartilage and the cricoid ring. These fractures are 
associated with edema of the endolarynx; this observa- 
tion can be helpful especially when the cartilages are not 
completely calcified, for example in young patients. 

Fractures 

Fractures of the cricoid cartilage usually cause the ring to 
eollapse. The anterior arch of the cricoid cartilage is 
pushed posteriorly into the airway. The thyroid cartilage 
can fracture vertically or horizontally. The vertical frac- 
ture is usually easily seen but horizontal fractures are in 
the plane of the axial image and can be missed. 
Hemorrhage in the adjacent pre-epiglottic fat may be a 
clue to this type of fracture. The arytenoid cartilage does 
not fracture but can be dislocated. 



Dislocations 

Dislocations can occur at the cricothyroid articulation or 
at the cricoarytenoid joint. Cricothyroid dislocation is 
usually associated with significant trauma. There is usu- 
ally a fracture of the inferior horn of the thyroid cartilage 
rather than a true dislocation. Cricoarytenoid dislocation 
may occur with minor trauma. The status of these joints 
can be difficult to determine at imaging, but the radiolo- 
gist should indicate if the cartilages appear to be normal- 
ly aligned. 

Conclusions 

At Massachusetts Eye and Ear Infirmary, we currently 
prefer CT for the evaluation of cancer of the larynx. MRI, 
however, has a slight advantage in evaluating vertical ex- 
tension, especially relative to the ventricle and in evalu- 
ating the cartilage. With newer and faster MRI sequences, 
this may change. For submucosal lesions, we use an en- 
hanced CT scan to differentiate among chondroid lesions, 
vascular lesions and laryngocele. For trauma, we use CT 
to look for fractures and dislocations. 



Suggested Reading 

Becker M, Zbaren P, Delavelle J et al (1997) Neoplastic invasion 
of the laryngeal cartilage: reassessment of criteria for diagno- 
sis at CT. Radiology 203:521-532 

Becker M (1998) Larynx and hypopharynx. Radiol Clin North Am 
36:891-920 

Castelijns JA, Becker M, Hermans R (1996) Impact of cartilage 
invasion on treatment and prognosis of laryngeal cancer. Eur 
Radiol 6:156-169 

Curtin HD (1989) Imaging of the larynx: current concepts. 
Radiology 173:1-11 

Curtin HD (2003) The larynx. In: Som PM, Curtin HD (eds) Head 
and neck imaging, 4th edn. Mosby, St. Louis, pp 1595-1699 

Zbaren P, Becker M, Lang H (1997) Staging of laryngeal cancer: 
endoscopy, computed tomography and magnetic resonance 
versus histopathology. Eur Arch Otorhinolaryngol 254[Suppl 
1]:S1 17-122 




IDKD 2004 



Imaging the Larynx and Hypopharynx 

M. Becker 

Department of ENT and Maxillofacial Radiology, Division of Diagnostic and Interventional Radiology, Geneva University Hospital, 
Geneva, Switzerland 



Introduction 

The larynx and hypopharynx are imaged with either 
computed tomography (CT) or magnetic resonance 
imaging (MRI). A standard CT examination is done in 
the supine position, and the patient is instructed to re- 
sist swallowing or coughing. Axial slices are obtained 
from the base of the skull to the trachea with a scan 
orientation parallel to the true vocal cords. lodinated 
contrast material (total dose, 35-40 g iodine) is given 
intravenously with an automated power injector. 
Images are obtained during quiet breathing rather than 
during apnea because the abducted position of the true 
vocal cords facilitates evaluation of the anterior and 
posterior commissures. Acquisitions with 3-mm colli- 
mation at pitch 1 and overlapping reconstruction inter- 
vals of 2 mm are the minimum parameters necessary to 
evaluate the larynx. With multislice CT scanners, a 
slice thickness of 1.3 mm and overlapping reconstruc- 
tions every 0.6 mm are used routinely by many inves- 
tigators, including myself, allowing high quality two- 
dimensional (2D) reconstructions in the coronal or 
sagittal plane. 

To date, MRI of the larynx and hypopharynx is per- 
formed using dedicated surface neck coils in phased- 
array (multicoil) configuration. Two basic pulse se- 
quences are currently used by most investigators, 
namely T1 -weighted and T2-weighted sequences. 
Axial T2-weighted fast spin echo (FSE) and Tl- 
weighted SE or FSE images are obtained with a scan 
orientation parallel to the true vocal cords. Typical im- 
age parameters include a slice thickness of 3-4 mm 
with a 0- 1 mm intersection gap, and a field of view of 
18x18 cm^ or less. The acquisition matrix should be 
256x512 cm^ or 512x512 cm^. Additional axial Tl- 
weighted images after intravenous administration of 
gadolinium chelates are obtained routinely. Fat-satu- 
rated T1 -weighted images with or without contrast en- 
hancement and fat-saturated T2-weighted images are 
optional. Images in the coronal or sagittal plane may 
be obtained in order to evaluate certain anatomic 
spaces, such as the preepiglottic space in the sagittal 



plane, or the paraglottic space and the ventricle in the 
coronal plane. 

The most common indications to perform cross-sec- 
tional imaging of the larynx include: 

1 . Squamous cell carcinoma 

2. Non-squamous cell tumors 

3. Cysts and laryngoceles 

4. Vocal cord paralysis 

5. Inflammatory lesions, and 

6. Traumatic lesions. 



Squamous Cell Carcinoma 

Over 90% of laryngeal and hypopharyngeal tumors are 
squamous cell carcinomas [1-17]. With few exceptions, 
squamous cell tumors are located at the mucosal surface, 
and the clinical diagnosis is readily confirmed by endo- 
scopic biopsy. However, submucosal tumor extension 
cannot be assessed reliably with endoscopy alone. 
Because the degree of infiltration into the surrounding 
deep anatomic structures has implications for treatment 
and prognosis, cross-sectional imaging with either CT or 
MRI is required for the diagnostic workup of laryngeal 
and hypopharyngeal tumors. Unusual malignant neo- 
plasms of the laryngohypopharyngeal region, such as 
chondrosarcomas, lymphomas and lipomas, are often en- 
tirely submucosal. The origin and extension of these tu- 
mors are difficult to diagnose with endoscopy, and plan- 
ning of biopsy and treatment usually depends on imaging 
findings. 

Patterns of Tumor Spread 

Carcinoma of the larynx arises in the supraglottic re- 
gion (30%), glottis (65%) or subglottic region (5%) 
[3, 6]. 

Supraglottic tumors originating from the epiglottis 
primarily invade the preepiglottic space. MRI diagnosis 
of tumor spread to the preepiglottic space is made when 
the high signal intensity of fat normally seen on the Tl- 
weighted image is replaced by a mass with low signal 




150 



M. Becker 





Fig. la-d. Neoplastic invasion of the preepiglottic space due to supraglottic cancer, a Axial 
contrast- enhanced CT image at the supraglottic level shows an enhancing mass invading the 
preepiglottic space (asterisk), b Axial unenhanced T1 -weighted image at the supraglottic 
level shows a tumor mass with an intermediate signal intensity as it extends into the 
preepiglottic space (dashed arrows). Note the high signal intensity of the noninvaded para- 
glottic space due to the high content of fatty tissue (thin arrows), c Axial Gd-enhanced Tl- 
weighted image at the same level shows enhancement of the tumor mass invading the 
preepiglottic space, d Whole-organ axial histologic slice from supraglottic horizontal laryn- 
gectomy specimen confirms tumor invasion of the preepiglottic space (arrows). Epiglottis 
(E), thyroid cartilage (T). (Reproduced from [6] with permission) 



intensity and when enhancement of the preepiglottic 
mass is observed (Fig. 1) [3, 6]. Although sagittal im- 
ages are best suited for delineating the extent of tumor 
spread within the preepiglottic space (Fig. 2), standard 
axial images are sufficient to establish the diagnosis. 
Similarly, on CT, the diagnosis of preepiglottic space 
invasion is made when an enhancing mass is seen with- 
in the preepiglottic fat (Fig. 1). Supraglottic tumors 
originating from the false cord, laryngeal ventricle, or 
aryepiglottic fold primarily infiltrate the paraglottic 
space. The primary sign of tumor spread to the para- 
gldttic space on MRI or CT is replacement of fatty tis- 
sue by tumor tissue (Fig. 2) [3, 6, 7]. The sensitivities 
of MRI and CT for the detection of neoplastic spread 
to the preepiglottic and paraglottic space are high; how- 
ever, the corresponding specificities are limited due to 
the fact that peritumoral inflammatory changes may 
lead to overestimation of tumor spread with both meth- 
ods, therefore resulting in false-positive assessments. 
The primary lymphatic spread of supraglottic carcino- 
mas is directed toward the superior jugular lymph 



nodes. Lymph node metastases are common and often 
bilateral. 

Glottic carcinoma typically arises from the anterior 
half of the vocal cord and primarily spreads into the an- 
terior commissure. Invasion of the anterior commissure is 
seen on CT and MRI as a soft tissue thickening of more 
than 1-2 mm. Once the tumor has reached the anterior 
commissure, it may easily spread into the thyroarytenoid 
muscle, contralateral cord, paraglottic space, supraglottis 
or subglottis. On axial CT or MR images, neoplastic in- 
vasion occurring at the subglottic level below the anteri- 
or commissure appears as an irregular thickening of the 
cricothyroid membrane. Further spread occurs mainly in 
a cephalad or caudad direction or, via the cricothyroid 
membrane, into the perilaryngeal tissue. Paraglottic tu- 
mor spread in glottic cancer may be entirely occult clini- 
cally and detectable only by means of CT or MRI. 
Subglottic spread is relatively common in glottic cancer 
and may either occur superficially or deep in the elastic 
cone. Deep subglottic spread is difficult to detect endo- 
scopically, and underestimation of the tumor may occur 




Imaging the Larynx and Hypopharynx 



151 




unless CT or MRI is performed. The degree of subglottic 
spread is best displayed on axial images (Fig. 3). Coronal 
images are of limited help in the assessment of subglot- 
tic spread, because they are difficult to interpret except in 
the midcoronal plane. Lymphatic metastases from glottic 
carcinoma are uncommon as long as the tumor is con- 
fined to the endolarynx. However, once the tumor has 
spread into the soft tissues of the neck, the frequency of 
lymph node metastases increases significantly. 

Primary subglottic carcinoma is uncommon and tends to 
spread to the trachea or invade the thyroid gland and the 
cervical esophagus. Lymph node metastases are much more 
common than in glottic carcinoma and they affect the para- 
tracheal and pretracheal nodes. These nodes drain to the 
lower jugular or upper mediastinal nodes. Cross-sectional 
imaging performed in patients with primary subglottic tu- 
mors should, therefore, include the upper mediastinum. 




Fig. 2a-c. Neoplastic invasion of the left paraglottic space due to 
ventricular cancer, Endoscopically only a very small mucosal le- 
sion was present within the left laryngeal ventricle, a Axial con- 
trast-enhanced CT image at the supraglottic level shows a tumor 
mass (T) invading the left paraglottic space. Note normal appear- 
ance of the contralateral paraglottic space {arrowhead), b Axial 
contrast-enhanced T1 -weighted image shows an enhancing tumor 
mass {arrows) invading the left paraglottic fat. Normal right para- 
glottic fat space {asterisk), c Whole-organ axial slice from speci- 
men confirms extensive paraglottic space invasion by a predomi- 
nantely submucosal tumor mass (7). The tumor mass originated 
from the left laryngeal ventricle {arrowhead). Curved arrow, right 
laryngeal ventricle. Note the normal aspect of the laryngeal mu- 
cosa overlying the tumor mass {thin arrows). (Reproduced from [7] 
with permission) 



Carcinoma of the hypopharynx may arise in the piriform 
sinus (65%), post-cricoid area (20%) and posterior pharyn- 
geal wall (15%) [3, 6]. Carcinoma of the piriform sinus is 
readily detected with endoscopy while very early superfi- 
cial spreading tumors that are limited to the mucosa may be 
invisible at cross-sectional imaging. In most cases, howev- 
er, patients with piriform sinus tumors initially present with 
advanced lesions and diagnosis with CT or MRJ is straight- 
forward. Because the piriform sinus is usually collapsed 
during quiet respiration, the exact tumor location (medial 
wall vs. lateral wall) may be difficult to determine radio- 
logically and a close cooperation with the head and neck 
surgeon is essential. Tumors originating from the lateral 
wall of the piriform sinus have a tendency to infiltrate ear- 
ly the soft tissues of the neck. Tumors originating from the 
medial wall or the angle of the piriform sinus may infiltrate 
the larynx by growing anteriorly into the paraglottic space. 






152 



M. Becker 




Fig. 3a-d. Neoplastic invasion of the cricoid cartilage. Glottosubglottic carcinoma of the larynx in a 46-year-old man. a Contrast-enhanced 
CT at the subglottic level shows a right-sided tumor mass adjacent to a sclerotic cricoid cartilage. Sclerosis suggests invasion of the adja- 
cent cricoid cartilage, b Axial T1 -weighted image. A mass with intermediate signal intensity infiltrates the right subglottic region. The right 
cricoid cartilage shows decreased signal intensity {arrowhead), c Contrast-enhanced axial T1 -weighted image shows extensive contrast en- 
hancement of the right subglottic tumor mass, as well as of the adjacent cricoid cartilage. The extensive enhancement of the right cricoid 
cartilage {arrowhead) suggests tumor invasion, d Axial slice from specimen at the same level shows a large subglottic tumor mass invad- 
ing the right cricoid cartilage {arrowheads). C, cricoid cartilage. (Reproduced from [1] with permission) 



Piriform sinus carcinoma frequently invades the paraglottic Carcinoma of the posterior pharyngeal wall common- 

space and the laryngeal cartilages (discussed later). ly involves both the oropharynx and hypopharynx. On 

Post-cricoid carcinoma is uncommon in general but ob- axial MR images, these tumors appear as asymmetrical 

served in certain groups at risk (e.g. patients with thickenings of the posterior pharyngeal wall. Invasion of 

Plummer-Vinson syndrome). These tumors spread submu- the prevertebral muscles is unusual at initial presentation, 
cosally most often toward the cervical esophagus. Because Squamous cell carcinoma of the hypopharynx has a rel- 
tumor growth is mainly submucosal, the true extent only atively poor prognosis, with up to 75% of patients having 
becomes apparent with axial or sagittal MR images. metastases to cervical lymph nodes at initial presentation. 






Imaging the Larynx and Hypopharynx 

Neoplastic Cartilage Invasion 

Invasion of the hyaline laryngeal cartilage by squamous 
cell carcinoma alters staging, prognosis and, in most cen- 
ters, the therapeutic approach [14, 6-12], Most authors be- 
lieve that radiation therapy cannot eradicate tumor within 
cartilage but may result in perichondritis and chon- 
dronecrosis, although some others believe that radiation 
therapy can sterilize tumor even in invaded cartilage. 
Invasion of the thyroid, cricoid and both arytenoid carti- 
lages precludes classic voice-sparing partial laryngectomy 
and necessitates total laryngectomy, an extremely invasive 
procedure. Recent direct comparison studies with histolog- 
ic correlation have shown that CT has a high sensitivity and 
a high negative predictive value for the detection of carti- 



153 

lage invasion provided that the following criteria are used: 
sclerosis, erosion, lysis and extralaryngeal spread [4]. 

- Sclerosis is a sensitive sign for the detection of neo- 
plastic cartilage invasion and enables diagnosis of ear- 
ly or microscopic intracartilaginous tumor spread (Fig. 
3). It corresponds to bone remodeling and new bone 
formation induced by the presence of tumor cells in 
immediate vicinity. The specificity of this sign varies 
considerably from one cartilage to another, and is low- 
est in thyroid cartilage (40%) and higher in cricoid and 
arytenoid cartilages (76% and 79%, respectively). 
Therefore, if a tumor mass is seen adjacent to a scle- 
rotic cartilage, this does not automatically imply that 
tumor cells are found within the remodelled marrow 
cavity (Fig. 4). Conversely, failing at surgery to re- 




Fig. 4a-d. Inflammatory changes appearing as false-positive neoplastic cartilage invasion on CT and MRJ. Glottosubglottic carcinoma of 
the larynx in a 71 -year-old woman, a Contrast-enhanced CT image shows sclerosis of the left cricoid cartilage suggesting invasion by the 
adjacent tumor, b T1 -weighted axial image. A mass with low signal intensity infiltrates the left subglottic region. The adjacent left cricoid 
cartilage shows decreased signal intensity (arrowhead), c Contrast-enhanced Tl-weighted image. Contrast enhancement is seen within the 
left cricoid cartilage (arrowhead), as well as within the subglottic tumor mass suggesting invasion, d Axial slice from specimen shows a 
large, left-sided subglottic tumor mass (7) but no evidence of cartilage invasion. The cricoid cartilage shows extensive inflammatory 
changes with lymph follicles (black arrow), fibrosis (asterisks) and bone resorption (open arrows), but with an intact perichondrium (white 
arrows). (Reproduced from [ 1 ] with permission) 






154 



M. Becker 



move a cartilage that exhibits sclerosis on CT carries 
a 50%-60% risk of leaving tumor behind. 

- As the process of cartilage invasion progresses, minor 
and major areas of osteolysis are seen within the areas 
of new bone formation. Minor areas of osteolysis cor- 
respond to the CT criterion of erosion, while major ar- 
eas of osteolysis correspond to the CT criterion of ly- 
sis. Histologically, erosion and lysis correspond to de- 
struction of bone due to osteoclastic activity. As a con- 
sequence, erosion and lysis can be considered specific 
criteria for the detection of neoplastic invasion in all 
cartilages. The overall specificity of erosion and lysis 
is 93%. However, both of these criteria are not very 
sensitive as they are bound to the presence of more ad- 
vanced invasion of laryngeal cartilage [4]. 

- Extralaryngeal spread occurs due to tumor invasion 
through a cartilage into the extralaryngeal soft tissues. 
This CT criterion is highly specific (overall specifici- 
ty, 95%), but because it is only seen very late in the 
disease process its sensitivity is as low as 44%. 

By applying the combination of sclerosis, erosion-ly- 
sis, and extralaryngeal spread to all cartilages, one may 
obtain an overall sensitivity as high as 91%. Because the 



negative predictive value of this combination is 95%, CT 
may be considered an excellent test to exclude cartilage 
invasion prior to treatment. 

MRI has a high sensitivity for the detection of cartilage 
invasion. The reported sensitivity of MRI for the detection 
of neoplastic cartilage invasion is 89%-94%. the specificity 
is 74%-88%, and the negative predictive value is 94%-96%. 
Extensive tumor invasion involving both inner and outer as- 
pects of the cartilage can be diagnosed with a high accura- 
cy with MRI. In addition, MRI enables detection of in- 
tracartilaginous tumor spread. If tumor is present only adja- 
cent to the inner aspect of a cartilage, the radiologist can dif- 
ferentiate between tumor and nonossified cartilage by com- 
paring the different MR pulse sequences. Cartilage invaded 
by tumor displays an intermediate or low signal intensity on 
T1 -weighted images, a higher signal intensity on proton- 
density and T2-weighted images, and areas of enhancement 
within the cartilage adjacent to the tumor after injection of 
gadolinium chelates (Fig. 3). If these signs are absent, car- 
tilage infiltration can be ruled out with a high level of con- 
fidence, since the negative predictive value of MRI is high 
(Fig. 5). Unfortunately, the MRI findings suggesting neo- 
plastic cartilage invasion are not as specific as expected ini- 





Fig. 5a-c. True-negative MRI findings for neoplastic invasion of 
the thyroid cartilage, a T1 -weighted image obtained at the supra- 
glottic level shows a right-sided piriform sinus tumor with inter- 
mediate to low signal intensity (7). The adjacent right thyroid lam- 
ina also has intermediate to low signal intensity {arrow), b Tl- 
weighted SE image obtained after intravenous administration of 
contrast medium shows contrast enhancement of the tumor mass 
(7), however no enhancement of the adjacent thyroid lamina {ar- 
row). This suggests that the thyroid cartilage is composed of 
nonossified hyaline cartilage and that no intracartilaginous tumor 
spread is present, c Corresponding axial slice from surgical speci- 
men at the same level confirms that the right thyroid lamina is 
composed of nonossified hyaline cartilage {arrows). No cartilage 
invasion was found at histological analysis. The tumor (7) arose 
from the lateral wall of the right piriform sinus. (Reproduced from 
[6] with permission) 





Imaging the Larynx and Hypopharynx 



155 



tially, but may be false positive in a considerable number of 
instances; the positive predictive value is only 71%. This is 
because reactive inflammation, edema, fibrosis, and ectopic 
red bone marrow in the vicinity of the tumor may display 
diagnostic features similar to those of cartilage infiltrated by 
tumor (Fig. 4). Since inflammatory changes are most com- 
mon in the thyroid cartilage, the specificity of MRI in de- 
tecting neoplastic invasion of the thyroid cartilage is only 
56%, as opposed to 87% and 95% in the cricoid and ary- 
tenoid cartilages, respectively [1]. The positive diagnosis of 
neoplastic invasion of the thyroid cartilage should, there- 
fore, be made with extreme caution at MRI. 

TNM Classification of Laryngeal and Hypopharyngeal 
Carcinomas 

Laryngeal and hypopharyngeal carcinomas are staged ac- 
cording to the criteria recommended by the International 
Union Against Cancer (UICC) or according those of the 
American Joint Cancer Committee (AJCC) [15]. The 
guidelines of both UICC and AJCC, which are now al- 
most identical, recommend the use of cross-sectional 
imaging. Several studies as well as experience at my in- 
stitution have shown that the use of CT or MRI greatly 
improves the accuracy of the pretherapeutic T classifica- 
tion of laryngeal and hypopharyngeal tumors. In our ex- 
perience, the overall pretherapeutic staging accuracy is 
80% with CT and 85% with MRI [6, 17]. 



Non-squamous Cell Laryngeal Neoplasms 

Carcinomas with other histological traits different from 
the squamous cell type occur only occasionally in the 
laryngohypopharyngeal region [2]. Adenocarcinoma and 
adenosquamous carcinoma typically originate and extend 
beneath the mucosal surface. Therefore, these carcinomas 
are more difficult to detect with endoscopy than squa- 
mous cell carcinoma. Although none of the unusual types 
of carcinoma has any signal characteristics allowing its 
distinction from squamous cell carcinoma on CT or MRI, 
the discrepancy between the presence of a tumoral soft 
tissue mass on MRI and an intact mucosa at endoscopy 
should always raise the suspicion of a non-squamous neo- 
plasm [2, 7]. In such cases, both CT and MRI serve not 
only to assess the degree of tumor spread, but also to di- 
rect the endoscopist to the appropriate site where to per- 
form deep, aggressive biopsies necessary to establish the 
correct histologic diagnosis. 

Laryngeal chondrosarcoma predominantly affects men 
in the sixth or seventh decade and more commonly orig- 
inates from the cricoid than from the thyroid cartilage [2, 
3, 16]. As in chondrogenic tumors of other locations, the 
tumor matrix has high signal intensity on T2-weighted 
images corresponding to hyaline cartilage with its low 
cellularity and high water content (Fig. 6). Small areas of 
low signal intensity correspond to stippled calcifications; 
these changes are, however, not as well demonstrated as 





Fig. 6a-d. CT and MRI appearances of chondrosarcoma of the thyroid cartilages in a 47- 
year-old man presenting with a hard lump in the neck, a Axial contrast-enhanced CT scan 
shows a large, lobulated mass with coarse and stippled calcifications characteristic of chon- 
drosarcoma (arrows), b T1 -weighted axial MR image shows a lobulated mass with low sig- 
nal intensity that arises from the right thyroid lamina (arrowheads). Note normal aspect of 
the left thyroid lamina, c T2-weighted FSE image. The tumor mass has high signal intensi- 
ty due to high water content. The hypointense areas within the tumor correspond to intratu- 
moral calcifications (arrowheads), d T1 -weighted contrast-enhanced, coronal image. 
Moderate peripheral enhancement (arrowheads). Note extramucosal tumor location. The pa- 
tient underwent voice-preserving laryngeal resection and he is free of recurrence five years 
later. (Panel a, reproduced from [6] with permission; panels b-d, reproduced from [2] with 
permission) 




156 



M. Becker 



with CT, where characteristic “popcorn” calcifications 
may be seen. Although the injection of gadolinium 
chelates may lead to a diffuse central or peripheral en- 
hancement on T1 -weighted images, these findings are 
non-specific and do not help in differentiating low-grade 
chondrosarcoma from benign chondroma [16], Although 
the diagnosis of laryngeal chondrosarcoma can be strong- 
ly suspected on CT or MRI, it must be confirmed with 
deep biopsy. Surgery is regarded as the treatment of 
choice and is increasingly done in the form of function- 
preserving laryngeal resection. Imaging studies are im- 
portant for follow-up after treatment, since chondrosar- 
coma has a tendency to recur locally. 

Cysts and Laryngoceles 

Laryngeal cysts arise from the mucosa and are related to 
minor salivary glands, whereas laryngoceles (also called 
saccular cysts) are dilatations of the saccule of the laryn- 
geal ventricle. A laryngocele occurs when there is ob- 
struction of the ventricle, sometimes by a small cancer lo- 
cated near the neck of the saccule. Laryngoceles may 
contain air or fluid. An internal laryngocele extends su- 
periorly in the paralaryngeal space, and may present as a 
submucosal supraglottic mass at endoscopic evaluation. 
If the laryngocele extends through the th}Tohyoid mem- 
brane into the soft tissues of the neck, it is called an ex- 
ternal laryngocele. On CT or MRI, a laryngocele presents 
as a well-circumscribed, air- or fluid-filled structure ex- 
tending from the laryngeal ventricle into the paralaryn- 
geal space or through the thyrohyoid membrane into the 
soft tissues of the neck. 



Vocal Cord Paralysis 

Paralysis of the recurrent laryngeal nerve is the most com- 
mon type of vocal cord paralysis. The CT and MRI fea- 
tures of recurrent laryngeal nerve paralysis are explained 
by atrophy of the thyroarytenoid muscle and include an 
enlarged ventricle, ipsilateral enlargement of the piriform 
sinus, and decreased size or fatty infiltration seen at the 
level of the true vocal cord. A patient with recurrent la- 
ryngeal nerve paralysis of unknown origin should under- 
go imaging of the entire pathway of the vagus and recur- 
rent laryngeal nerves to exclude a tumor mass. 

Inflammatory Lesions 

Epiglottitis and croup are diagnosed clinically and do 
not require imaging. In the Western Hemisphere, the 
larynx is rarely affected by granulomatous diseases. 
Tuberculosis, numerous mycotic infections, leprosy 
and syphilis appear to be more common in Asia and 
Africa and may affect the larynx and pharynx. 
Relapsing polychondritis affects laryngeal cartilages. 



and rheumatoid arthritis affects the cricoarytenoid and 
the cricothyroid joints. 

Necrotizing fasciitis of the head and neck is a severe, 
acute, and potentially life-threatening bacterial soft tissue 
infection with a rapid clinical evolution [5]. It affects 
both immunocompetent and immunocompromised pa- 
tients and, unless immediate surgical treatment is given, 
leads invariably to mediastinitis and fatal sepis. CT and 
MRI findings include cellulitis, multiple fluid collections 
with or without gas in various neck compartments, dif- 
fuse enhancement of neck fasciae and myositis. The in- 
flammatory, edematous process often involves the larynx, 
necessitating intubation. Myositis with or without ab- 
scess formation or myonecrosis is seen in the pharyngeal 
constrictor muscles. In the acute and subacute phases, CT 
and MRI may demonstrate contrast enhancement of the 
pharyngeal constrictor muscles or frank disruption of the 
pharyngeal wall. 

Trauma 

Trauma to the larynx can cause mucosal tears, submu- 
cosal hematomas, avulsion of the epiglottis, fractures of 
the laryngeal cartilages, and joint dislocation [3]. Both 
fractures and hematomas may lead to severe airway com- 
promise. Fractures of the thyroid cartilage may be verti- 
cal or horizontal, or the entire thyroid cartilage may be 
shattered (Fig. 7). Fractures of the cricoid cartilage tend 
to occur bilaterally. Cricothyroid dislocations tend to oc- 
cur with severe trauma, while cricoarytenoid dislocations 
tend to occur with minor trauma. Most patients with la- 
ryngeal trauma undergo CT, which allows excellent de- 
lineation of most traumatic lesions. However, MRI may 
provide significant additional information in young pa- 
tients, in whom laryngeal cartilages are not ossified and 
therefore not well visualized on CT. 




Fig. 7. Laryngeal trauma following motor vehicle accident. 
Comminutive fracture of the thyroid cartilage (arrows) and bilat- 
eral fracture of the cricoid cartilage (thin arrows) 




Imaging the Larynx and Hypopharynx 



157 



Stenosis of the larynx or cervical trachea can be a se- 
quela of trauma or prolonged intubation. MRI (axial, 
coronal and sagittal images) and CT with 2D reconstruc- 
tions are useful in exactly defining the vertical extent of 
a stenosis. 



References 

1. Becker M, Zbaren P, Laeng H et al (1995) Neoplastic invasion 
of the laryngeal cartilage: comparison of MRI and CT with 
histopathologic correlation. Radiology 194:661-669 

2. Becker M, Moulin G, Kurt AM et al (1998) Non-squamous 
cell neoplasms of the larynx: radiologic-pathologic correla- 
tion. Raiographics 18(5): 1189-1209 

3. Becker M (2004) The larynx. In: Valvassouri G, Mafee M, 
Becker M (eds) Imaging of the head and neck. Thieme, New 
York Stuttgart, in press 

4. Becker M, Zbaren P, Delavelle J et al (1997) Neoplastic inva- 
sion of the laryngeal cartilage: reassessment of criteria for di- 
agnosis at CT. Radiology 203:521-532 

5. Becker M, Zbaren P, Hermans R et al (1997) Necrotizing 
fasciitis of the head and neck: role of CT in diagnosis and 
management. Radiology 202:471-476 

6. Becker M (1998) Larynx and hypopharynx. Radiol Clin N Am 
36:891-920 

7. Becker M (2001) Malignant lesions of the larynx and hy- 
popharynx. In: Baert AL, Sartor K, Hermans R (eds) Imaging 
of the larynx. Springer, Berlin Heidelberg New York, pp 55-84 



8. Becker M, Moulin G, Kurt AM et al (1998) Atypical squamous 
cell carcinoma of the larynx and hypopharynx: radiologic fea- 
tures and pathologic correlation. Eur Radiol 8:1541-1551 

9. Castelijns JA, Gerritsen GJ, Kaiser MC et al (1988) Invasion 
of laryngeal cartilage by cancer: comparison of CT and MRI. 
Radiology 167:199-206 

10. Castelijns JA, Becker M, Hermans R (1996) The impact of car- 
tilage invasion on treatment and prognosis of laryngeal cancer. 
Eur Radiol 6:156-169 

11. Castelijns JA, van den Brekel MWM, Tobi H et al (1996) 
Laryngeal carcinoma after radiation therapy: correlation of ab- 
normal MRI signal patterns in laryngeal cartilage with the risk 
of recurrence. Radiology 198:151-155 

12. Curtin HD (1996) The larynx. In: Som PM, Curtin HD (eds) 
Head and neck imaging, 3rd edn. Mosby, St. Louis, pp 612-707 

13. Loevner LA, Yousem DM, Montone KT et al (1997) Can ra- 
diologists accurately predict preepiglottic space invasion with 
MRI? AJR Am J Roentgenol 169:1681-1687 

14. Mancuso AA (1991) Evaluation and staging of laryngeal and 
hypopharyngeal cancer by computed tomography and magnet- 
ic resonance imaging. In: Silver CE (ed) Laryngeal cancer. 
Thieme, New York Stuttgart, pp 46-94 

15. Sobin LH, Wittekind C (2002) TNM classification of malig- 
nant tumors, 6th edn. UICC, Wiley-Liss, New York 

16. Stiglbauer R, Steurer M, Schimmerl S et al (1992) MRI of car- 
tilaginous tumors of the larynx. Clin Radiol 46:23-27 

17. Zbaren P, Becker M, Laeng H (1996) Pretherapeutic staging of 
laryngeal cancer: clinical findings, computed tomography and 
magnetic resonance imaging versus histopathology. Cancer 
77(7): 1263-1273 




IDKD 2004 



Paranasal Sinuses and Nose: Normal Anatomy and Pathologic Processes 

L.A. Loevner 

Neuroradiology Division, Department of Radiology, University of Pennsylvania Medical Center, Philadelphia, PA, USA 



Introduction 

The development of the paranasal sinuses has been well 
described [1]. The maxillary sinuses are the first of the 
paranasal sinuses to develop; development begins in the 
first trimester of gestation and usually is completed by 
.adolescence. The ethmoid air cells arise from numerous 
evaginations from the nasal cavity, beginning with the 
anterior air cells, and progressing to the posterior air 
cells. The ethmoid air cells begin to develop between the 
end of the first trimester and the mid-second trimester of 
gestation, and reach final adult proportions during pu- 
berty. The sphenoid sinus is present by the second 
trimester, and is fully developed in early adolescence. 
The frontal sinuses are the only sinuses consistently ab- 
sent at birth. Their development is variable: it begins 
during the first few years of life and completes in ado- 
lescence. 

The paranasal sinuses and nasal cavity are lined by 
ciliated columnar epithelium that also has mucinous and 
serous glands. The common drainage pathway for the 
frontal sinuses, maxillary sinuses, and anterior ethmoid 
air cells is through the paired ostiomeatal complex made 
up of the maxillary sinus ostium, the infundibulum, the 
hiatus semilunaris, and the middle meatus [2]. 
Secretions within the maxillary sinuses circulate to- 
wards the maxillary sinus ostium propelled by ciliated 
epithelium. From the maxillary ostium, mucous circu- 
lates through the infundibulum located lateral to the un- 
cinate process (an osseous extension of the lateral nasal 
wall). From the infundibulum, secretions progress 
through the hiatus semilunaris, an air-filled channel an- 
terior and inferior to the ethmoidal bulla (the largest 
ethmoid air cell), and then pass into the middle meatus, 
the nasal cavity, and the nasopharynx where they are 
swallowed. 

The frontal sinuses drain inferiorly through the frontal 
ethmoidal recess (the channel between the inferomedial 
frontal sinus and the anterior part of the middle meatus) 
into the middle meatus (the common drainage site also 
for the anterior ethmoid air cells that have ostia in con- 
tact with the infundibulum of the ostiomeatal complex) 



[2]. The anterior-most ethmoid air cells, the agger nasi 
cells, are located in front of the middle turbinates, which 
are in turn located anterior, lateral, and inferior to the 
frontal ethmoidal recess. Inconstant ethmoid air cells lo- 
cated along the anterosuperior maxillary surface just in- 
ferior to the orbital floor are called maxilloethmoidal or 
Haller cells. 

The posterior ethmoid air cells are located behind 
the middle turbinate; secretions drain through the su- 
perior and supreme meatus, and through other tiny os- 
tia under the superior turbinate into the sphenoeth- 
moidal recess, the nasal cavity and finally the na- 
sopharynx. Secretions in the sphenoid sinus are pro- 
pelled by cilia to the ostia of this sinus that is located 
above the sinus floor. 

The three sets of turbinates in the nasal cavity include 
the superior, middle, and inferior turbinates. Occasionally 
there may be a supreme turbinate located above the su- 
perior turbinate. When the middle turbinate is aerated, it 
is termed a concha bullosa, present in up to 30%-50% of 
patients. Large or opacified conchae bullosa may ob- 
struct the ostiomeatal complex. 

The nasal septum separates the right and left nasal 
turbinates, dividing the nasal cavity in half. The ante- 
rior and inferior aspects of the nasal septum are made 
of cartilage. The posterior portion of the nasal septum 
is osseous. The superoposterior portion is the perpen- 
dicular plate of the ethmoid bone, while the inferopos- 
terior portion is the vomer. The nasal septum is lined 
by squamous epithelium, while the remainder of the 
nasal cavity is lined by columnar epithelium. There is 
normal cyclical passive congestion and decongestion 
of each side of the nasal cavity and ethmoid air cells 
that result in temporary mucosal thickening in these 
structures [2]. The nasolacrimal duct extends from the 
lacrimal sac at the medial canthus along the anterior 
and lateral nasal walls, and drains into the inferior 
meatus. 

Blood supply to the sinonasal structures comes from 
both the internal and external carotid arteries. The arter- 
ial supply to the frontal sinuses is from supraorbital and 
supratrochlear branches of the ophthalmic artery, while 




Paranasal Sinuses and Nose: Normal Anatomy and Pathologie Processes 



159 



venous drainage is through the superior ophthalmic 
veins. The ethmoid air cells and sphenoid sinus receive 
blood from branches of the sphenopalatine artery (aris- 
ing from the external carotid circulation) as well as from 
the ethmoidal branches of the ophthalmic artery (arising 
from the internal carotid circulation). Venous drainage is 
through nasal veins into the nasal cavity, or through eth- 
moidal veins that drain into ophthalmic veins, which 
subsequently drain into the cavernous sinus. The maxil- 
lary sinuses are supplied predominantly by branches of 
the maxillary artery from the external carotid circula- 
tion, and drain through facial and maxillary veins, the 
latter communicating with the pterygoid venous plexus. 
It is the venous drainage of the paranasal sinuses (ulti- 
mately communicating with the cavernous sinus and 
pterygoid venous plexus) that is responsible for the po- 
tential intracranial complications of sinusitis including 
meningitis, subdural empyema, and cavernous sinus 
thrombosis. 



Disease Processes of the Paranasal Sinuses 

Congenital Lesions 

Many congenital abnormalities of the nasal cavity and 
skull base are related to aberrant invagination of the 
neural plate [3]. During neural plate retraction in em- 
bryogenesis, the dura contacts the dermis. Normally this 
dermal connection regresses; when it does not congeni- 
tal abnormalities that may develop include sinus tracts, 
dermoid cysts, encephaloceles (Fig. 1), and nasal 
gliomas [3, 4]. With nasal gliomas (not true neoplasms), 
there is a fibrous connection with the intracranial com- 
partment. 




Fig. 1. A 47-year-old patient with recurrent right nasal drainage. 
Coronal CT image shows a defect in the right cribriform plate {ar- 
row). Soft tissue (E) in the adjacent right sinonasal cavity repre- 
sents an encephalocele 



Inflammatory Disease and Sinusitis 

Most cases of acute sinusitis are related to an antecedent 
viral upper respiratory tract infection. Swelling of the 
mucosal surfaces within the paranasal sinuses results in 
apposition, leading to obstruction of the normal drainage 
pathways and inadequate drainage that results in bacteri- 
al overgrowth. 

When evaluating patients for sinusitis and potential 
fundoscopic sinus surgery (FESS), it is important to 
evaluate certain anatomical landmarks. Specifically, 
the medial orbital walls, cribiform plate, and roof and 
lateral walls of the sphenoid sinus should be evaluated 
for osseous defects or thinning. A defect in the lamina 
papyracea may result in orbital penetration and subse- 
quent hematoma formation or optic nerve injury, 
whereas a dehiscence in the cribiform plate or sphenoid 
sinus can result in meningitis, encephalocele (Fig. 2), 
or carotid artery complications (perforation, pseudoa- 
neurysm). It is important to comment on mucosal ap- 
position or inflammatory changes in the region of the 
ostiomeatal unit and the sphenoethmoidal recess. The 
presence of air-fluid levels should be noted. 
Hyperdense secretions on computed tomography (CT) 
may suggest the presence of inspissated secretions or 
fungal disease [5]. 

Sinonasal secretions have variable signal intensity pat- 
terns on magnetic resonance imaging (MRI) related to 
the protein concentration and mobile water protons with- 
in the secretions [6]. The changes in signal intensity are 
likely due to extensive cross-linking of glycoproteins pre- 
sent within hyperproteinaceous secretions. As a result, 
the amount of mobile water protons decreases. When the 
protein concentration is less than 10%, secretions are hy- 
pointense on T1 -weighted images and hyperintense on 
T2-weighted images (this is the state in which there is a 
high concentration of free mobile water). When protein 
concentrations approach 20%-25%, they typically are hy- 
perintense on both unenhanced T1 -weighted (Fig. 3b) and 
T2-weighted sequences. When protein concentrations ex- 
ceed approximately 25%, they are typically hypointense 
on T2-weighted images, and when they exceed 28%, they 
are hypointense on both T1 -weighted and T2-weighted 
sequences. 

Complications of sinusitis include periorbital cel- 
lulitis, meningitis, thrombophlebitis (including cav- 
ernous sinus thrombosis), subdural empyema, brain 
abscess, and perineural and perivascular spread of in- 
fection (in particular in invasive fungal disease). 
Infectious “mycotic” aneurysms of the intracranial 
vasculature are uncommon, accounting for less than 
5% of intracranial aneurysms. The causative organism 
is usually bacterial, although these lesions may occur 
as a complication of invasive sinonasal fungal infec- 
tion [7]. Mucoceles may be a complication of sinusitis 
and are most common in the frontal sinuses and eth- 
moid air cells. Mucoceles show a spectrum of signal 
characteristics on MRI that are dependent on their pro- 




160 



L.A. Loevner 




Fig. 2a, b. A 41 -year-old man with encephalocele complicating 
functional endoscopic sinonasal surgery, a Unenhanced coronal 
T1 -weighted MR image shows an osseous defect in the left frontal 
sinus and floor of the anterior cranial fossa with an encephalocele 
(arrows) extending into the adjacent sinonasal cavity, b Sagittal 
T2-weighted MR image shows the large defect in the floor of the ^ 




anterior cranial fossa with the encephalocele (arrows). There are 



secretions and fluid in the frontal sinus (*) 



Fig. 3a, b. A 33-year-old man with squamous cell carcinoma of the 
sinonasal cavity and orbital extension, a Coronal CT image shows 
osseous destruction of the superolateral nasal wall and marked 
thinning and medial bowing of the medial right orbital wall (ar- 
rows). There is also absence of the bone comprising the floor of the 
right frontal sinus (open arrow), b Unenhanced coronal T1 -weight- 
ed MR image shows tumor (7) in the right sinonasal cavity (isoin- 
tense to brain), hyperintense proteinaceous secretions (white ar- 
rows) in the right frontal sinus, and soft tissue stranding (black ar- 
rows) in the extraconal fat in the medial right orbit 




Paranasal Sinuses and Nose; Normal Anatomy and Pathologic Processes 



161 



tein content, and usually demonstrate rim enhancement 
compared to tumors that typically show more solid en- 
hancement (Fig. 4) [8-11]. 




Sinonasal Neoplasms 

CT and MRI play complementary roles in evaluating 
sinonasal tumors. CT provides bone detail, while MRI 
provides superior soft tissue resolution. MRI is better in 
evaluating intracranial extension of neoplastic processes. 
Another advantage of MRI over CT is its ability to help 
discern complex sinonasal secretions and inflammatory 
disease from malignancy [8-11]. 

Typically, benign lesions such as mucoceles and be- 
nign neoplasms when large enough expand the paranasal 
sinus that they are in and remodel the adjacent bone on 
CT (Fig. 4b). Occasionally, malignant tumors have be- 
nign imaging features. The contrary is also true, i.e. be- 
nign tumors may appear to be relatively aggressive [12- 
14]. Caution is always required when evaluating masses 
within the sinuses. Fibro-osseous lesions that involve the 
paranasal sinuses include osteomas (Fig. 5), fibrous dys- 
plasia, ossifying or nonossifying fibromas, and chon- 
droid lesions. These can be difficult to diagnose on MRI 
as the abnormal osseous structures may appear hy- 
pointense like “air” (Fig. 6), but fibro-osseous lesions 
frequently have characteristic sclerotic appearances on 
CT (Fig. 5) [15]. 




Fig. 4a, b. A 38-year-old man with extensive mucoceles compli- 
cating prior facial trauma, a Enhanced axial T1 -weighted MR im- 
age shows multiple, expansile, rim-enhancing mucoceles in the 
frontal sinuses. The wide spectrum of T1 -weighted signal intensi- 
ties is due to differing protein concentrations, b Corresponding un- 
enhanced axial CT image shows multiple expansile lesions in the 
frontal sinuses with associated long-standing osseous remodeling 
and expansion 



Fig. 5. Coronal CT image of bone detail shows a characteristic os- 
teoma of the left frontal sinus. The benign neoplasm of osseous ori- 
gin is intrasinus with heterogenous fibrous and sclerotic bone matrix 



162 



L.A. Loevner 



Most neoplasms may be distinguished from inflamma- 
tory conditions due to their imaging characteristics as well 
as their more solid enhancement pattern (compared to rim 
enhancement in benign inflammatory disease). In addi- 
tion, T2-weighted images may be helpful as most malig- 
nancies are heterogeneous and intermediate in signal in- 
tensity compared to inflammatory secretions that tend to 
be hyperintense and more homogeneous in character [8]. 




Fig. 6a, b. Nonossifying fibroma of the left ethmoid air cells, a 
Axial T2-weighted MR image shows intermediate signal intensity 
of the ventral portion of the mass (short arrows), and hypointensi- 
ty of the posterior portion of the mass mimicking “air” (long ar- 
rows). b Unenhanced axial T1 -weighted image shows expansile 
mass of the left ethmoid. The ventral portion is isointense to mus- 
cle (short arrows). The posterior portion is markedly hypointense 
(isointense to air in the adjacent paranasal sinuses, long arrows), 
consistent with sclerotic bone. There is lateral bowing of the me- 
dial orbital wall with lateral displacement of the adjacent medial 
rectus muscle and optic nerve 




Fig. 7. Squamous cell carcinoma of the paranasal sinuses. 
Intracranial extension through the floor of the anterior cranial fos- 
sa (arrow) and right medial intraorbital extension are shown on this 
fat-suppressed coronal T1 -weighted MR image 



In most instances, excellent anatomic resolution may be 
acquired from an unenhanced and enhanced MRI examina- 
tion performed with a standard head coil. Imaging of 
sinonasal malignancies must include high-resolution views 
not only of the sinonasal cavity, but also of the orbit, skull 
base, and intracranial compartment (Figs. 3, 7) [11, 16]. 
Direct extension or perineural spread of tumor may allow for 
tumor extension outside the sinonasal cavity and into these 
important adjacent anatomic locations, which significantly 
impacts upon the patient’s staging and operability, the type 
of resection that will occur, and the necessity for radiation 
therapy (Tables 1, 2). An especially important anatomic lo- 
cation for detection of tumor spread is the pterygopalatine 
fossa. When tumor spreads to the pterygopalatine fossa, ex- 
tension to the adjacent orbit, infratemporal fossa (masticator 
space), skull base, and intracranial compartment may subse- 
quently occur. Specifically, tumor may spread from the 
pterygopalatine fossa to the pterygomaxillary fissure, al- 
lowing subsequent growth into the infratemporal compart- 
ment. From the pterygopalatine fossa, tumor may extend to 



Table 1. Criteria for nonresectability of sinonasal malignancies. 
Depending upon the institution, cavernous sinus and optic chiasm 
invasion are relative contraindications for surgery 



Distance metastases 

Invasion of the optic chiasm 

Extensive cerebral involvement 

Bilateral cavernous sinus or carotid infiltration 

Poor general medical conditions 





Paranasal Sinuses and Nose: Normal Anatomy and Pathologic Processes 



163 



Table 2. T system for staging sinonasal malignancies, according 
to the American Joint Committee on Cancer (Adapted from [22]) 



T1 Neoplasm confined to anthral mucosa without associated os- 
seous erosion or destruction 

T2 Neoplasm with erosion or destruction of the osseous infra- 
structure, including the hard palate or middle nasal mediatus 

T3 Tumor extension to the anterior ethmoid air cells or posterior 
wall of the maxillary sinus, or tumor invasion outside of the 
sinonasal cavity to involve the skin of the cheek or floor or 
medial wall of the orbit 

T4 Tumor extension to the posterior ethmoid air cells, sphenoid 
sinus, pterygoid plates, nasopharynx, base of skull or cribi- 
form plate, or tumor involving the contents within the orbit 



the vidian canal, and from here to foramen lacerum, and 
then into the intracranial compartment. In addition, tumor 
may spread from the pterygopalatine fossa to the foramen 
rotundum, and in such cases patients may present with a 
fifth cranial nerve neuropathy. From the foramen rotundum, 
tumor may spread in a perineural fashion to the inferior or- 
bital fissure, and into the orbit or ventral cavernous sinus. 

Papillomas arise from columnar epithelium and in- 
clude three common subtypes: inverted, cylindric, and 
fungiform [12]. Papillomas tend to occur unilaterally in 
the sinonasal cavity. The most common papilloma is the 
inverted papilloma. These are more common in men in 
the fourth through sixth decades of life. This is a benign 
neoplasm; however, squamous carcinoma may be present 
within these in up to 20% of cases. Inverted papillomas 
may have an aggressive appearance with bone destruc- 
tion, and occasionally they may erode the skull base (as 
may benign polyps), simulating an aggressive cancer [13, 
14]. This neoplasm typically arises from the lateral nasal 
wall at the level of the middle turbinate, or less com- 
monly, within the maxillary sinus [12, 13]. 

Squamous cell carcinoma is the most common malig- 
nancy of the paranasal sinuses and nasal cavity, represent- 
ing two-thirds of all cancers here [11, 12, 17]. Occupation- 
al exposures to radium, Thorotrast, and nickel are causative 
factors. The majority arise in the maxillary sinus anthrum 
[17], while the next most common site is the septum in the 
nasal cavity. Adenocarcinomas, lymphoma, undifferentiat- 
ed carcinomas, esthesioneuroblastomas [18], and sarcomas 
may also occur in the sinonasal cavity. Following squa- 
mous cell carcinoma, minor salivary gland tumors [19] and 
melanomas [20] (arising from melanocyte rests in the mu- 
cosa) are the next most common malignancies to affect the 
nasal cavity. Minor salivary gland tumors represent a wide 
spectrum of histologic subtypes including adenoid cystic 
carcinoma (most common), mucoepidermoid carcinoma, 
and acinic cell carcinomas [11, 19]. Uncommon, but like- 
ly to be recognized more frequently as patients live longer, 
is post-transplantation lymphoproliferative disorder of the 
paranasal sinuses, seen in the setting of chronic immuno- 
suppression following organ transplantantation [21]. This 
is usually aggressive (lymphoma), and may mimic invasive 
fungal sinusitis (Fig. 8). Treatment is usually a combina- 




Fig. 8. A 5 3 -year-old man with post-transplantation lymphoprolif- 
erative disorder (non-Hodgkin’s lymphoma) complicating lung 
transplantation 8 years previously. The patient presented with mul- 
tiple acute cranial nerve palsies. Enhanced axial T1 -weighted MR 
image shows fluid in the right sphenoid sinus, tumor (7) in the left 
sphenoid sinus with disruption of the left lateral sphenoid sinus 
wall (black arrows), and abnormal enhancing tissue (lymphoma) in 
the left middle cranial fossa (white arrows) and in the infratempo- 
ral fossa and masticator spaces (M) 



tion of irradiation and chemotherapy. Metastatic disease to 
the sinuses is unusual, with renal cell carcinoma the most 
commonly reported. 

References 

1. Schaeffer JP (1920) The embryology, development and anato- 
my of the nose, paranasal sinuses, nasolacrimal passageways 
and olfactory organs in man. Blakiston’s Son, Philadelphia 

2. Zinreich SJ, Kennedy DW, Kuman AJ et al (1988) MR imag- 
ing of normal nasal cycle: comparison with sinus pathology. J 
Comput Assist Tomogr 12:1014-1019 

3. Barkovich AJ, Vandermarch P, Edwards MSB et al (1991) 
Congenital nasal masses: CT and MR imaging features in 16 
cases. AJNR Am J Neuradiol 12:105-1 16 

4. Kallman JE, Loevner LA, Yousem DM, Chalian AA, Lanza 
DC, Jin L, Hayden RE (1996) Heterotopic brain in the ptery- 
gopalatine fossa. AJNR Am J Neuroradiol 18:176-179 

5. Babbel RW, Harnsberger HR, Sonkens J et al (1992) Recurring 
patterns of inflammatory sinonasal disease demonstrated on 
screening sinus CT. AJNR Am J Neuroradiol 13:903-912 

6. Dillon KB, Som PM, Fullerton GD (1990) Hypointense MR 
signal in chronically inspissated sinonasal secretions. 
Radiology 174:73-78 

7. Hurst RW, Judkins A, Bolger W, Chu A, Loevner LA (2001) 
Mycotic aneurysm and cerebral infarction resulting from fun- 
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Neuroradiol 22:858-863 

8. Som PM, Shapiro MD, Biller HF et al (1988) Sinonasal tumors 
and inflammatory tissues: differentiation with MR. Radiology 
167:803-808 

9. Lanzieri CF, Shah M, Krauss D et al (1991) Use of gadolini- 
um-enhanced MR imaging for differentiating mucoceles from 
neoplasms in the paranasal sinuses. Radiology 178:425-428 




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10. Loevner LA, Yousem DM, Lanza DC, Kennedy DW, Goldberg 
A (1995) MR evaluation of frontal osteoplastic flaps using au- 
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Neuroradiol 16:1721-1726 

1 1 . Loevner LA, Sonners AI (2002) Imaging of neoplasms of the 
paranasal sinuses. Magn Reson Imaging Clin N Am 10:467- 
493 

12. Lasser A, Rothfeld PR, Shapiro RS (1976) Epithelial papillo- 
ma and squamous cell carcinoma of the nasal cavity and 
paranasal sinuses: a clinicopathologic study. Cancer 38:2503- 
2510 

13. Woodruff WW, Vrabec DP (1994) Inverted papilloma of the 
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AJR Am J Roentgenol 162:419-423 

14. Som PM, Lawson W, Lidov MW (1991) Simulated aggressive 
skull base erosion in response to benign sinonasal disease. 
Radiology 180:755-759 

15. Tobey JD, Loevner LA, Yousem DM, Lanza DC (1996) 
Tension pneumocephalus: a complication of invasive ossifying 
fibroma of the paranasal sinuses. AJR Am J Roentgenol 
166:711-713 

16. Eisen MD, Yousem DM, Loevner LA, Thaler ER, Bilkner WB, 



Goldberg AN (2000) Preoperative imaging to predict orbital 
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17. St. Pierre S, Baker SR (1983) Squamous cell carcinoma of the 
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513 

18. Som PM, Lidov M, Brandwein M et al (1994) Sinonasal es- 
thesioneuroblastoma with intracranial extension: marginal tu- 
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Neuroradiol 15:1259-1262 

19. Sigal R, Monnet 0, de Baere T et al (1992) Adenoid cystic car- 
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184:95-101 

20. Yousem DM, Li C, Montone KT, Montgomery L, Loevner LA, 
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IDKD 2004 



Nose, Paranasal Sinuses and Adjacent Spaces 

R. Maroldi*, D. Farina^ R Nicolai^ 

' Department of Radiology, University of Brescia, Brescia, Italy 
^ Department of Otorhinolaryngology, University of Brescia, Brescia, Italy 



Introduction 

Cross-sectional imaging has achieved an essential role 
in the diagnosis and treatment planning of both inflam- 
matory and neoplastic diseases of the sinonasal tract. 
Particularly, the development of endonasal surgery tech- 
niques during the last two decades has been possible as 
a result of the detailed preoperative assessment of the 
extent of lesions and of the individual anatomy of the 
nose and paranasal sinuses, usually by computed to- 
mography (CT). With multislice CT, reliable informa- 
tion in the sagittal plane is obtained, making the assess- 
ment of key structures, such as the frontal recess, more 
feasible. 

External surgical approaches still have a role in the 
management of selected cases of inflammatory diseases 
and benign tumors, and are considered the gold standard 
for malignant tumors. In this setting, magnetic resonance 
imaging (MRI) maintains a primary role, as its superior 
contrast resolution enables clinicians to more clearly dif- 
ferentiate normal tissues and structures from adjacent le- 
sions. Improvements in both time and spatial resolutions 
of the new MRI equipment help minimize the rate of non- 
diagnostic examinations, and enable an accurate demon- 
stration even of the thin and complex anatomic structures 
of the sinonasal area. Therefore, MRI is generally used to 
obtain a precise pretreatment assessment of intraorbital 
or intracranial invasion. 

Nowadays, a multidisciplinary approach to the com- 
plex variety of sinonasal lesions is considered the best 
strategy to a successful management of these diseases. 
Consequently, thorough knowledge of the essential infor- 
mation for planning endonasal and external approaches is 
necessary. 

Essential Anatomy of the Sinonasal Area 

Three anatomic areas, corresponding to the narrowest 
tracts of drainage pathways, are crucial for endoscopic 
surgery plaiming: the ostiomeatal complex, the frontal re- 
cess, and the spheno-ethmoid recess. 



The ostiomeatal complex is the crossroads of anterior 
ethmoid, frontal sinus and maxillary sinus mucus drainage. 
It includes the maxillary sinus ostium, the ethmoid in- 
fundibulum, the ethmoid bulla and the uncinate process. 
The ethmoid infundibulum is the air passage connecting 
the maxillary sinus ostiiun to the middle meatus. It is bor- 
dered superiorly by the ethmoid bulla, the most posterior 
cell within the anterior ethmoid, protruding in the middle 
meatus. The vertical portion of the uncinate process is a 
key structure of the ostiomeatal complex (Figs. 1-4). 




Fig. 1. Multislice CT with coronal multiplanar reconstruction 
shows key structures of the ostiomeatal complex. The ethmoid bul- 
la (B) faces the uncinate process {UP), and borders the ethmoidal 
infundibulum {small circles). Both the ethmoidal infundibulum and 
the frontal recess {interrupted arrows) empty into the middle mea- 
tus {asterisks). The thin horizontal {small opposite arrows) and ver- 
tical {VL) cribriform plates appear less dense than the thicker orbital 
plate of the frontal bone. FE, fovea ethmoidalis; MS, maxillary si- 
nus; FS, frontal sinus; O, maxillary sinus ostium; MT, middle 
turbinate; IT, inferior turbinate; H, inferior orbital “Haller” cells 




166 



R. Maroldi, D. Farina, R Nicolai 




Fig. 2a-c. Multislice CT in axial plane, a The plane crosses the skull base at the level of the body of the sphenoid bone. The vidian canal 
(VQ, foramen ovale (FO), spinosum (FS), lacerum (FL), and nasolacrimal duct (NLD) are shown. Large pneumatized middle turbinate 
(M7) on left side, b Anterior attachment of the uncinate process onto the nasolacrimal duct wall is demonstrated. The ethmoidal in- 
fundibulum empties between the uncinate process (arrowheads) and the ethmoid bulla (B). Lateral attachment of the middle turbinate 
(ground lamella, GL) marks the limit between anterior and posterior ethmoidal sinuses, c A few millimeters above, the bulla appears larg- 
er. Part of the superior turbinate (ST) is shown. CC, carotid canal 




Fig. 3a-f. Three-dimensional gradient echo enhanced (VIBE) sequence in the coronal plane, 0.5-mm sections, a The most anterior eth- 
moidal cell is the agger nasi cell (A), medially bordered by the pneumatized vertical lamella of the middle turbinate, b The vertical por- 
tion of the uncinate process (vUP) attaches superiorly at the fovea ethmoidalis. c Ethmoidal infundibulum (opposite arrowheads) and frontal 
recess (interrupted arrow) empty into the middle meatus (asterisks). Opposite arrows point to the sandwich-like appearance of the “nasal 
mucosa-medial maxillary wall-maxillary sinus mucosa” complex, d A large ethmoid bulla (B) on left side, a pneumatized vertical lamella 
of the middle turbinate on right side; lamellar concha (asterisk), e Posterior to the ethmoid bulla, the retrobullar space is seen on the left 
(arrows)’, attachment of the ground lamella (GL) on the right, f Right sphenoid sinus (SS) and superior turbinates (ST) are detected. IT, in- 
ferior turbinate; MT, middle turbinate; NLD, nasolacrimal duct; CG, crista galli; FS, frontal sinus; o, maxillary sinus ostium; MS, maxil- 
lary sinus; FE, fovea ethmoidalis 






Nose, Paranasal Sinuses and Adjacent Spaces 



167 




Fig. 4. Multislice CT in sagittal plane through the frontal recess {in- 
terrupted arrow) passing posteriorly to the agger nasi (A) and anteri- 
orly to the anterior ethmoidal cells, the ethmoid bulla (B) being the 
largest. Posterior ethmoidal cells (PBQ are located behind the ground 
lamella (GL) of the middle turbinate (MT). IT, inferior turbinate; ST, 
superior turbinate; FS, frontal sinus; SS, sphenoid sinus 



Depending on the type of its superior attachment, the 
frontal recess (i.e. the mucus drainage path of the frontal si- 
nus) may open into the middle meatus medially or into the 
uncinate process laterally [1]. Correct assessment of the 
frontal recess opening is essential in planning the proper en- 
donasal approach to the frontal recess and the adequate ex- 
posure of the frontal sinus. Medially, the middle turbinate 
borders the ostiomeatal complex; its vertical lamina is an- 
chored on the cribriform plate while its ground lamella in- 
serts laterally onto the posterior part of lamina papyracea. 

The spheno-ethmoid recess is outlined by the anterior 
sphenoid sinus wall and by the posterior wall of posteri- 
or ethmoid cells. It conveys sphenoid sinus secretions in 
the superior meatus; it is more clearly shown on axial CT 
images. 

Several variants of sinonasal anatomic structures may 
be observed. Most of them are due to the variable extent 
of ethmoid sinus pneumatization into adjacent sinuses - 
infra-orbital ethmoidal cells, frontal cells and Onodi cells 
derive, respectively, from pneumatization of maxillary, 
sphenoid and frontal sinuses. Other anatomic variants are 
created by pneumatization of bones adjacent to the eth- 
moid as the agger nasi cells from lacrimal bone and the 
supraorbital ethmoid cells from frontal bone. Finally, 
pneumatization of laminae belonging to the ethmoid 
bone itself give rise to concha bullosa. Extensive 
pneumatization of the sphenoid sinus may result in de- 



hiscence of its bony boundary with the internal carotid 
artery or the optic nerve. Similarly, dehiscences of the 
lamina papyracea increase the risk of complications due 
to damage of intraorbital structures. 

The pterygopalatine fossa is a narrow space between 
the pterygoid process and the vertical process of the pala- 
tine bone (merged with the posterior maxillary sinus 
wall). Both CT and MRI demonstrate the foramina and 
canals, through which the pterygopalatine fossa directly 
communicates with: the middle cranial fossa (vidian canal 
and foramen rotundum); the orbit (inferior orbital fissure); 
the masticatory space (pterygomaxillary fissure); the 
choana (sphenopalatine foramen); and the oral cavity 
(greater and lesser palatine canals). Within the ptery- 
gopalatine fossa are the pterygopalatine ganglion, part of 
the maxillary nerve, terminal branches of the internal 
maxillary artery (the sphenopalatine artery), and fat. 

Imaging Patients with Acute and Chronic 
Rhinosinusitis 

Acute rhinosinusitis does not require radiological studies 
of the paranasal sinuses because documenting the pa- 
tient’s symptoms and performing an endoscopic exami- 
nation are sufficient for a correct diagnosis [2]. Contrast- 
enhanced CT is indicated in the suspicion of an orbital 
complication (generally secondary to acute ethmoiditis) 
or an intracranial complication. CT may help discrimi- 
nate among preseptal cellulitis, subperiosteal inflamma- 
tion and intraorbital (extra- or intraconal) spread [3]. 
Overall, CT permits a correct diagnosis of orbital com- 
plications in up to 91% of cases, and is significantly more 
accurate than clinical examination alone (81%) [4]. 

Intracranial complications are generally secondary to 
frontal sinusitis. They are observed even in the absence 
of sinus wall defects because they may be secondary to 
thrombophlebitis of valveless diploic veins [5]. Imaging 
is mandatory for correctly assessing the degree of in- 
volvement of intracranial structures. In this setting, MRI 
is considered the technique of choice because its accura- 
cy is superior to that of CT, in particular in differentiat- 
ing dural reaction from epidural, subdural or intracerebral 
abscess and in demonstrating thrombosis of sagittal or 
cavernous sinus [4, 6]. 

CT evaluation of patients complaining of chronic rhi- 
nosinusitis and nasal polyposis is essentially focused on 
accurate delineation of the extent of the lesion and of 
those elements (e.g. inflammatory mucosal changes and 
predisposing anatomic factors) that may impair mucocil- 
iary drainage (Fig. 5). 

Patients affected by chronic rhinosinusitis should re- 
ceive adequate medical treatment before CT examination 
of the paranasal sinuses, in order to treat acute infection 
and resolve mucosal edema. Oral antibiotics, nasal steroids 
and antihistamines, prescribed at least three weeks before 
CT, decrease the risk of overestimating chronic inflamma- 
tion and polypoid reaction of the mucosa. 




168 



R. Maroldi, D. Farina, R Nicolai 




Fig. 5. Single-slice coronal CT image of a patient with chronic rhi- 
nosinusitis reveals infundibular pattern, mucosal thickening along 
maxillary walls, and both ethmoidal infundibula without blockage 
of mucus drainage 



one of these patterns is based on the obstruction of dif- 
ferent mucus-drainage pathways: 

1 . Infundibular pattern is mainly due to the presence of 
mucosal thickenings or isolated polyps along the eth- 
moid infundibulum with blockage of maxillary sinus 
drainage alone. 

2. Ostiomeatal unit pattern reflects the obstruction of all 
drainage systems in the middle meatus, leading to 
maxillary, frontal, and anterior ethmoid sinusitis. Most 
frequent causes are non-specific mucosal thickenings 
and nasal polyps. This pattern may also be observed in 
the presence of benign or malignant neoplasms arising 
from the lateral nasal wall. 

3. Spheno-ethmoid recess pattern is rather rare and con- 
sists of sphenoid sinusitis or posterior ethmoiditis, sec- 
ondary to spheno-ethmoid recess obstruction. 

4. The pattern of nasal polyposis is usually characterized 
by bilateral involvement of middle meatus, ethmoidal 
infundibulum and paranasal cavities by inflammatory 
polyps. At CT, they appear as solid lobulated lesions 
filling the ethmoidal sinus, the nasal fossae and sinusal 
cavities. Bone remodelling is associated, triggered by 
mechanical pressure exerted by the polyps but also by 
the local release of inflammatory mediators and by bac- 
terial invasion of bone and periosteum [10] (Fig. 6). 



Because of the high contrast between air, mucosa and 
bone, low-dose protocols may be adopted using single- 
slice CT (SSCT) equipment and decreasing the tube cur- 
rent to 30-50 mA [7]. This results in a considerable de- 
crease of the eye-lens dose [8] without a significant loss 
of diagnostic information. With multislice CT (MSCT), 
patient exposure is a primary issue, as recent data demon- 
strate eye-lens doses higher than with single-slice scan- 
ners, even when low-dose protocols are used. 

With SSCT, images are primarily acquired on the coro- 
nal plane, as perpendicular as possible to the hard palate 
by tilting the gantry and encouraging the patient to coop- 
erate. This plane permits demonstrating patency, width, 
and morphology of the middle and superior meatus and 
the ethmoidal infundibulum, which are hidden by 
turbinates and therefore difficult to access at clinical ex- 
amination. Moreover, coronal imaging clearly shows both 
the superior and lateral insertions of the middle turbinate, 
and the cribriform plate. In our experience, optimal 
demonstration of the ostiomeatal unit and of natural 
drainage pathways is achieved with: 

- Thin slice collimation (1-2 mm), to minimize partial 
volume artifacts that may mimic mucosal thickening 
along small-caliber drainage pathways, and 

- Scanning with 3- or 4-mm increments and 1.5 pitch 
(sequential or single-slice spiral equipment, respec- 
tively) as a trade-off between dose reduction and the 
necessity of not missing anatomical structures such as 
the uncinate process. 

According to Sonkens et al. [9], five different patterns 
of chronic rhinosinusitis may be described at CT. All but 




Fig. 6. Single-slice coronal CT image of a patient with chronic rhi- 
nosinusitis and nasal polyposis reveals air within the maxillary si- 
nuses. The normal signal of the ethmoidal sinuses and nasal cavi- 
ties has been replaced by soft tissue density. Outward bowing and 
thickening of both laminae papyraceae are due to the pressure ex- 
erted by polyps. A mucocele developing within the left frontal si- 
nus is secondary to drainage blockage. Resorption of the orbital 
roof and superior frontal sinus wall is present {arrows) 






Nose, Paranasal Sinuses and Adjacent Spaces 



169 



Widening of the ethmoidal infundibulum and trunca- 
tion of the middle turbinates (observed bilaterally in 
up to 80% of cases) are signs indicating nasal polypo- 
sis. A peculiar variant of sinonasal polyp is the antro- 
choanal polyp, which arises from the maxillary sinus 
and bulges into the middle meatus, where it extends 
between the middle turbinate and the lateral nasal wall 
to reach the choana. CT density of an antrochoanal 
polyp is low (fluid-like), while MRI appearance re- 
sembles that of inflammatory polyps. Because the 
waist of the polyp may be strangled as it passes 
through constrictive ostia, dilation and stasis of feed- 
ing vessels combined with edema lead the lesion to 
show non-homogeneous enhancement, a sign of an an- 
giomatous polyp [11]. 

5. Sporadic pattern includes a wide list of different con- 
ditions (such as isolated sinusitis, retention cyst, mu- 
cocele, post-surgical changes) unrelated to impairment 
of any of mucociliary drainage patterns. CT findings 
consist of partial or complete obliteration of a sinusal 
cavity by means of thickened mucosa with smooth, oc- 
casionally lobulated surface and homogeneously low 
density [12]. 



Imaging Patients with Fungal Rhinosinusitis 
and Aggressive Inflammatory Lesions 

Fungal infections may manifest in different forms that are 
grouped as noninvasive or invasive, according to the ab- 
sence or presence of fungal invasion of mucosa, submu- 
cosa, vessels and bone. 

- Noninvasive forms, generally occurring in immuno- 
competent patients, consist of fungus ball (mycetoma) 
and allergic fungal sinusitis (AFS). The CT and MRI 
appearances of fungus ball are conditioned by the 
high content of heavy metals and calcium within fun- 
gal hyphae. Therefore, fungus ball is spontaneously 
hyperdense at CT [13, 14], while both T2- and Tl- 
weighted sequences demonstrate a hypointense lesion 
bordered by hyperintense (T2) and enhancing (Tl, af- 
ter contrast administration) mucosa [6]. In some cas- 
es, TI and T2 shortening may be so relevant to result 
in signal void, making discrimination between fungus 
ball and intrasinusal air nearly impossible. AFS is cur- 
rently considered an immune disorder rather than an 
infectious disease. The combination of immunologic 
predisposing factors and drainage pathways obstruc- 
tion (due to chronic rhinosinusitis, nasal polyposis) 
leads to accumulation of allergic eosinophilic mucin 
within sinusal cavities. Intrasinusal fungal material as 
well as progressive dehydration of eosinophilic mucin 
produces CT and MRI patterns similar to fungus ball 
[14, 15]. 

- Acute fulminant and chronic courses are the two most 
frequent forms of invasive mycoses. A third rarer inva- 
sive form has been referred to as “indolent” fungal rhi- 
nosinusitis. Imaging findings of acute fulminant my- 



cosis consist of aggressive destruction of bony sinusal 
walls and invasion of adjacent soft tissues [16] charac- 
terized by ischemic necrosis. CT and MRI appearances 
of chronic and indolent forms are not yet clearly de- 
fined. In these varieties, the diagnosis is primarily 
based on the less aggressive clinical course, as com- 
pared to acute fulminant form. 

Imaging Patients with Sinonasal Masses: 

CT and MRI Techniques 

The first step in the diagnostic work-up of both benign 
and malignant sinus neoplasms consists of fiberoptic 
examination. Endoscopy allows adequate demonstra- 
tion of the superficial spread of the lesion and may 
guide biopsy. The discrimination between benign and 
malignant tumors and the precise characterization of 
the lesion are, in most cases, far beyond the capabili- 
ties of CT [17]. Main goals of imaging are, therefore, 
to provide a precise map of deep tumor extension in 
all areas blinded at fiberoptie examination, especially 
the anterior cranial fossa, orbit and pterygopalatine 
fossa. 

In this setting, MRI is the technique of choice because 
it clearly differentiates tumor from retained secretions, it 
allows early detection of perivascular and perineural 
spread, and provides higher contrast resolution. On the 
other hand, the strengths of CT consist of a superior def- 
inition of bone structures even in the case of subtle ero- 
sions, faster and easier performance, superior accessibil- 
ity and inferior costs. 

Despite the relevant improvements provided by multi- 
slice technology (e.g. fast coverage of the volume of in- 
terest, thin collimation, and acquisition of nearly isotrop- 
ic voxels), CT is nowadays restricted to patients not pre- 
liminarily examined by the otolaryngologist (to rule out 
non-neoplastic lesions) and to those with contraindica- 
tions to MRI. 

A key point of the MRI protocol is represented by 
spatial resolution: nasal cavity and paranasal sinuses 
are a complex framework of airspaces bordered by thin 
bony boundaries. Moreover, a thin osteoperiosteal lay- 
er separates the sinonasal region from the anterior cra- 
nial fossa (cribriform plate and dura) and the orbit 
(lamina papyracea and periorbita). An adequate depic- 
tion of these structures mandates high-field equipment 
and a dedicated circular coil (head coil). In addition, a 
high-resolution matrix (512x512) should be applied 
along with the smallest field of view (FOV) achievable. 
It is also recommended to acquire images not exceed- 
ing 3. 0-3. 5 mm in thickness, with an interslice gap 
ranging from 1.5 to 2.4 mm (50%-70%). These para- 
meters, applied to both turbo spin echo (TSE) T2- 
weighted and SE Tl -weighted sequences, represent an 
acceptable compromise between the need to attain 
small pixel size and the risk of significantly decreasing 
signal-to-noise ratio. 




170 



R. Maroldi, D. Farina, R Nicolai 



Inverted Papilloma and Juvenile Angiofibroma: 
CT and MM Findings 

Inverted papilloma (IP) is a benign epithelial neoplasm 
characterized by the infolding of the mucosa in the under- 
lying stroma without crossing the basement membrane. It 
is one of the most common benign neoplasms of the 
sinonasal tract [18, 19]. Its association with sinonasal ma- 
lignancies, in particular squamous cell carcinoma, is well 
established (incidence, I.5%-56%). IP may be suspected 
whenever an isolated, unilateral polypoid lesion is detect- 
ed by imaging studies. At CT, IP appears as a mass with 
soft-tissue density, non-homogeneous contrast enhance- 
ment and calcifications that represent residues of involved 
bone [20]. TSE T2-weighted and enhanced T1 -weighted 
images may reveal a pattern described as “septate striated 
appearance” [21], “convoluted cerebriform pattern” [22] or 
“columnar pattern” that corresponds to the peculiar macro- 
architecture of the lesion. The juxtaposition of several ep- 
ithelial and stromal layers results in a quite regular colum- 
nar pattern on MRJ: the first layer is hypointense on TSE 
T2-weighted images (because it is highly cellular) and 
mildly enhancing on post-contrast SE T1 -weighted im- 
ages; the second layer is hyperintense on TSE T2-weight- 
ed images (because it is edematous) and highly enhancing 
on post-contrast SE T I -weighted images. Thin SE Tl- 
weighted sections and acquisition of slices in the three 
planes of space improve the detection of this pattern. 

Juvenile angiofibroma (JA), a lesion composed of vas- 
cular and fibrous elements, typically occurs in adolescent 
males. It has been recently suggested that the lesion must 
be considered a vascular malformation [23] (or hamar- 
toma) rather than a tumor. Peculiar findings of JA are its 
tendency to grow in the submucosal plane and early in- 
vasion of cancellous bone of the pterygoid root, from 
which the lesion may grow laterally into the greater wing 
of the sphenoid bone. From its site of origin in the ptery- 
gopalatine fossa, the JA extends: (a) medially into the 
nasal cavity (and nasopharynx) via enlargement and ero- 
sion of the sphenopalatine foramen; (b) anteriorly with 
bowing of the maxillary sinus wall [24]; (c) laterally via 
the pterygomaxillary fissure; and (d) superiorly into the 
apex of the orbit through the inferior orbital fissure, and 
into the middle cranial fossa via the superior orbital fis- 
sure (Fig. 7). Enhanced CT and MRI provide a precise 
map of the extent into these spaces by detecting the en- 
hancing “finger-like projections” of JA, characterized al- 
so by sharp and lobulated margins. 

At CT, intradiploic spread may be demonstrated by 
differentiating the normal medullary content from the 
strongly enhancing JA. On MRI, this discrimination may 
be achieved by combining a plain T I -weighted image 
with a post-contrast T I -weighted image without or with 
fat saturation. The latter permits easy distinction of the 
hyperintense enhanced JA from the suppressed signal of 
the surrounding bone marrow. Intracranial extent is main- 
ly due to finger-like projections running along canals or 
through foramina. Rarely does it occur through the de- 




Fig. 7. Single-slice axial CT image of a juvenile angiofibroma 
with non-homogeneous enhancement occupying the sphenoid si- 
nuses. Displacement and thinning of the anterior wall (arrowheads) 
are due to a secondary mucocele. Intracranial extradural extent of 
the enhancing lesion runs through the right superior orbital fissure 
(arrows) 

struction of the inner table of the greater wing or the lat- 
eral sphenoid sinus walls. 



Essential Information in Managing Nasosinusal 
Neoplasms 

Although infrequent, sinonasal neoplasms are character- 
ized by numerous, different histotypes, a distinctive fea- 
ture which reflects the peculiar density of diverse 
anatomic structures present in this area. About 80% arise 
from the maxillary sinus (up to 73% are squamous cell 
carcinoma [25]), and most of the remaining tumors arise 
from the ethmoid sinus [26]; among these malignancies, 
adenocarcinoma, squamous cell carcinoma and olfactory 
neuroblastoma are prevalent. As a result, patterns of tu- 
mor spread may be generalized into two different models, 
according to their site of origin (e.g. maxillary area vs. 
naso-ethmoidal area). 

Mapping Maxillary Sinus Malignancies 

The critical areas of neoplasms arising from the maxillary 
area include the posterior wall of the maxillary sinus, the 
infratemporal and pterygopalatine fossae, and the orbital 
floor. The main goal of imaging is to assess the integrity of 
the bone-periosteal barrier. MRI is less accurate than CT in 
the assessment of focal bony erosions, since its calcium 
content cannot be adequately detected [27, 28]. 
Nevertheless, the most effective barrier to spread of ag- 
gressive lesions beyond sinusal walls is the periosteum 
rather than the mineralized bony walls [29]. Therefore, neo- 
plastic spread beyond the periosteum of the sinusal walls is. 



Nose, Paranasal Sinuses and Adjacent Spaces 



171 




Fig. 8a, b. Maxillary sinus squamous cell carcinoma, a Enhanced multislice CT image in coronal plane, b VIBE sequence in coronal plane. 
Both imaging techniques show the subperiosteal extent of tumor, covered by residual mucosa {black arrows). Invasion of the hard palate, 
nasal septum, right nasal floor, medial wall of the left maxillary sinus, and left zygomatic bone is demonstrated. Periosteal thickening at 
the orbital floor is shown on MRI (a). Residual bone at the left alveolar process is appreciated on CT (b) 



in effect, the critical information for therapeutic planning 
because it is related to extrasinusal infiltration (Fig. 8). 

The thin sinusal walls appear hypointense in every MR 
sequence because of the reduced water contents of corti- 
cal bone and periosteum. The entire thickness of the wall 
can be appreciated when invested by thickened mucosa or 
when the air on one or both sides has been replaced by 
mucous secretions or neoplastic tissue [30]. Of course, 
the proper frequency-encoding direction has to be select- 
ed in order to avoid asymmetric appearance of cortical 
bone due to chemical shift artifact [31]. 

Pterygopalatine Fossa Invasion: CT and MRI 
Findings 

Posterior spread into the pterygopalatine fossa is a rele- 
vant element in treatment planning. On MRI, neoplastic 
invasion of the pterygopalatine fossa is suspected when- 
ever its fat content has been replaced or effaced by soft 
tissue intensity [32]. Pterygoid canal and nerve, foramen 
rotundum and maxillary nerve are well demonstrated on 
axial and coronal MR sequences. Segmental thickening 
or asymmetric enhancement of the nerves may raise the 
suspicion of perineural spread [33]. Perineural spread 
has a significant impact on therapeutic planning: it is as- 
sociated with poor prognosis, and a reduction of more 
than 30% of the local control rate has been reported [34]. 
In fact, progression of tumor along trigeminal nerve 
branches may lead to cavernous sinus invasion. In this 
case, MRI shows enlargement, lateral bulging, and re- 
placement of the hyperintense venous signal by the tu- 
mor on coronal and axial T2-weighted and on enhanced 
T I -weighted sequences. Encasement of the internal 



carotid artery may also be detected on both Tl- and T2- 
weighted sequences. 

Mapping Naso-ethmoidal Malignancies 

In managing naso-ethmoidal neoplasm, the most critical 
areas include the orbit (particularly the roof and the pos- 
terior lamina papyracea where most postoperative recur- 
rences occur), the floor of the anterior cranial fossa), and 
the sphenoid sinus. Nowadays, even though its bony walls 
have been completely eroded, the orbit is preserved at 
surgery, on condition that the periorbita is not (or is min- 
imally) invaded. In fact, it has been recently demonstrat- 
ed that a more aggressive approach does not improve sur- 
vival [35]. 

Displacement and distortion of orbital walls by eth- 
moidal neoplasms occur frequently. The mineral content 
of the wall may be partially or completely resorbed, lead- 
ing to a questionable CT evaluation. On MRI, when a thin 
and regular hypointense area is still detectable - between 
neoplasm and orbital fat - the periorbita should be con- 
sidered intact. The assessment of the integrity of the pe- 
riorbita, however, it is not crucial since in most cases the 
lamina itself is partly or completely resected at surgery 
for intra-operative pathologic examination. Nevertheless, 
if imaging suggests orbital infiltration, the patient should 
be informed that orbital exenteration may be required. 
Assessment of invasion of the anterior cranial fossa floor 
has a great impact on surgical planning. 

Similarly to orbital wall invasion, bone destruction of the 
skull base is better demonstrated by CT. However, at the 
skull base level, imaging findings differ from those ob- 
served at other bone interfaces of the paranasal sinuses. 




172 



R. Maroldi, D. Farina, R Nicolai 



This is because when the skull base is invaded, the dura 
mater usually shows abnormal thickening and enhancement 
that can be due either to neoplastic invasion or to an in- 
flammatory, non-neoplastic reaction. Since dural invasion 
implies both a worse prognosis and a surgical resection not 
limited to the eroded bone, the goals of imaging focus on 
determining the depth of skull base invasion [36, 37], 

MRI has been reported to be more precise than CT. At 
the anterior cranial fossa level, a key aspect regards the 
analysis of the MRI signal intensity of the structures lo- 
cated at the interface between the ethmoid roof (below) 
and brain (above): the cribriform plate and its double pe- 
riosteal covering (lower layer); the dura mater (middle 
layer), and the subarachnoid space (superior layer). On 
enhanced sagittal and coronal SE T1 -weighted se- 
quences or 3D gradient echo (GE) fat-saturated Tl- 
weighted (VIBE) sequences, the three layers compose a 
“sandwich” of different signals (bone-periosteum com- 
plex, dura mater, cerebrospinal fluid) [38]. When a 
sinonasal neoplasm abuts against the cribrifom plate in- 
terface, without interrupting its hypointense signal, the 
lesion should be considered limited to the ethmoid and 
nasal fossae. Replacement of this lower layer hy- 
pointense signal by tumor implies bone-periosteum pen- 
etration. In this case, a thickened enhancing dura mater 
(middle layer) usually borders the neoplasm. If uninter- 
rupted, the neoplasm may be graded as intracranial-ex- 
tradural. Conversely, focal or more extensive replace- 
ment of enhanced, thickened dura mater by tumor indi- 
cates intracranial-intradural invasion. Brain invasion is 
suspected in the presence of edema [17] (Fig. 9). 




Fig. 9. Adenocarcinoma of the ethmoid sinus revealed by sagittal 
T1 -weighted spin echo image after gadolinium administration. 
Ethmoid and nasal fossae are occupied by a non-homogeneous en- 
hancing mass. At the level of the planum sphenoidalis, the tumor 
{white arrows) replaces the h)7pointense signal of bone {opposite 
black arrows) and the hyperintense signal of the thickened dura 
{single black arrow), suggesting intracranial intradural extent 



Determination of the resectability of tumors invading 
the brain does not stand only upon the assessment by 
imaging of the depth of tumor extent into the brain or on 
the detection of bilateral brain invasion. It requires a thor- 
ough evaluation of several other issues, the most impor- 
tant being the histotype and patient’s status. Patients with 
limited brain invasion treated by craniofacial resection 
have a nonsignificantly shorter mean survival compared 
to those with dural invasion only. 

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IDKD 2004 



Degenerative Diseases of the Spine 

B.C. Bowen 

Neuroradiology Section, MRI Center, Department of Radiology, University of Miami School of Medicine, Miami, FL, USA 



Degenerative Disk Disease 

The intervertebral disk consists of three components: car- 
tilaginous endplate (hyaline cartilage), nucleus pulposus 
(fibrocartilage with ground substance containing 
hyaluronic acid and glycosaminoglycans), and anulus fi- 
brosus (inner part contains fibrocartilage, while the outer 
part has dense fibrous lamellae with fibers, called Sharpey 
fibers, that insert on the vertebral ring apophysis). The in- 
ner part of the anulus and the nucleus pulposis are indis- 
tinguishable on magnetic resonance imaging (MRI). In the 
normal adult disk, a hypointense band or cleft is observed 
at the center of the nucleus pulposus and inner anulus on 
T2-weighted sagittal images and has been attributed to a 
higher concentration of collagen in this region of the disk. 
The adult disk normally lacks innervation and vascularity. 

With aging, the composition of the disk changes. 
Increases in collagen and decreases in glycosaminogly- 
cans are believed responsible for a decrease in hy- 
drophilicity and hence a decrease in water content, which 
results in a small (few percent) decrease in the signal in- 
tensity of the disk on T2-weighted images. Considerable 
loss of signal and loss of normal intervetebral disk height 
are not considered typical of normal aging, but rather in- 
dicate disk degeneration. The outer anulus manifests 
small concentric and transverse tears as part of normal 
aging; however, radial tears are considered a marker of 
disk degeneration. Concentric tears are characterized as 
delamination of the lamellae of the anulus fibrosus, and 
transverse tears represent disruptions of the anulus near 
the insertion of Sharpey fibers into the ring apophysis. 
The radial tear involves all layers of the anulus and ap- 
pears on MRI as a band of hyperintensity penetrating the 
normally hypointense outer anulus on T2-weighted im- 
ages and as a strip of enhancement on post-contrast Tl- 
weighted images. Contrast enhancement on MRI has 
been attributed to the ingrowth of granulation tissue into 
the tear as a consequence of healing. The clinical signif- 
icance of anular tears is not known. Some investigators 
attribute back pain in patients without nerve root com- 
pression to scar tissue within an annular tear or to a disk 
herniation that irritates nerve endings in the peripheral 



anulus (“diskogenic pain”). Many patients, though, have 
asymptomatic annular tears, suggesting that additional 
factors play a role in back pain. Nerves, which may be 
nociceptors, have been identified in the vertebral end- 
plates, facet joints, posterior longitudinal ligament (PLL), 
and anterior longitudinal ligament (ALL), thus enabling 
these structures to be potential sources of pain. 

Disk Degeneration 

Although the pathogenesis of intervertebral disk degen- 
eration is not well understood, the results of this process 
are characterized by loss of height, loss of signal intensi- 
ty, bulging or herniation of the disk [1]. These morpho- 
logical changes are consistently accompanied by the' an- 
ular tears described previously, and occasionally gas or 
calcification develops within a degenerating disk. A clas- 
sification system for lumbar disk degeneration based on 
routine T2-weighted MRI has been developed and shown 
to be reliable in distinguishing among grades of degener- 
ation based on intra- and interobserver kappa statistics 
[2]. Grades ranging from I (normal) to V (collapsed disk 
space) are assigned based on disk signal intensity, disk 
structure, distinction between nucleus and annulus, and 
disk height. Recent studies [3] have attempted to relate 
such grading schemes for disk degeneration to the bio- 
mechanical characteristics of individual lumbar motion 
segments subjected to loading forces in the direction of 
flexion-extension, axial rotation, or lateral bending. 

In addition to the degenerative changes involving the 
disk structure, biochemical and structural changes also oc- 
cur within the bone marrow near the endplates of the ver- 
tebral bodies adjacent to the degenerating disk [4]. These 
so-called endplate changes have been classified into three 
types, and some authors have proposed adding this classi- 
fication to the disk degeneration grading scheme in order 
to further specify degenerative disease. On MRI, the sig- 
nal intensity within the marrow bordering the endplate 
may be increased or decreased compared to normal mar- 
row. The combination of signal intensity changes on Tl- 
weighted and T2-weighted images reflects the underlying 




Degenerative Diseases of the Spine 



175 



histopathological changes and has been categorized by 
Modic, Ross, and others as type I, II, or III endplate 
changes. For type I changes (low signal intensity on Tl- 
weighted and high intensity on T2-weighted images), fi- 
brovascular tissue replaces the hematopoietic and lipid el- 
ements of normal marrow. Type I changes may mimic the 
MRJ findings for vertebral osteomyelitis; however, os- 
teomyelitis is usually accompanied by diskitis, resulting in 
an abnormal configuration and high signal intensity of the 
intervertebral disk space. These disk space abnormalities 
differ from the usual observation of low signal intensity for 
the degenerated disk; however, some degenerated disks 
contain cystic areas that are bright on T2-weighted images 
and thus may be indistinguishable from early infection. 

For type II changes (high signal intensity on T1 -weight- 
ed images and intermediate-high intensity on T2-weighted 
images), there is an increase in the lipid content of the mar- 
row space (i.e. more “yellow marrow”) compared to nor- 
mal. Type II changes are slightly more common than type 
I. The signal intensity on T2-weighted images depends in 
part on the pulse sequence used - the fast spin echo se- 
quence typically yields higher signal than the standard spin 
echo sequence. Type I changes have been observed to con- 
vert to type II changes with time, while type II changes are 
relatively stable. Type III changes most likely represent ar- 
eas of marrow replacement by dense woven bone, since 
type III changes correspond to areas of bony sclerosis on 
radiographic studies. On post-contrast T1 -weighted im- 
ages, the regions of type I or type II change may enhance 
with gadolinium, mimicking infection. 

Although there is no universally accepted classification 
system for describing degenerative disk disease, a stan- 
dardized nomenclature for classifying morphological 
changes in lumbar disk degeneration, focused on the pos- 
terior aspect of the disk, has been accepted and endorsed 
by a number of North American medical societies [5]. In 
this nomenclature, disks are either bulging or herniated. A 
bulging disk is one in which disk tissue extends diffusely 
(50%-100% of the total circumference of the disk) beyond 
the margins of the vertebral endplates. The anulus remains 
grossly intact. Herniated disks are subclassified into pro- 
trusions and extrusions, which may be focal (<25% of 
disk circumference) or broad-based (25%-50% of disk 
circumference). At least one study has shown that the fre- 
quency of protrusions (27%) is much greater than the fre- 
quency of extrusions (1%) in asymptomatic patients. 

A protrusion has a roughly conical shape, so that the 
distance between edges of the disk material extending be- 
yond the vertebral endplates is narrower than the distance 
between the edges at the base of the protrusion. 
Anatomically, some of the outer anular fibers remain in- 
tact; however, identification of these fibers on MRI or 
computed tomography (CT) is difficult or impossible. In 
an extrusion, the distance between the edges of the disk 
material extending beyond the vertebral endplates is 
wider than the distance at the base in at least one plane 
of view. In other words, extrusion is identifiable when the 
portion (“cap”) of the herniated disk beyone the end- 



plates is wider than the “neck” connecting the cap to the 
bulk of the disk in the interspace. An extrusion is a larg- 
er herniation than a protrusion and extends through the 
entire anulus. MRI is not accurate in determining whether 
the extruded disk also disrupts the PLL. A sequestration 
is a specific form of extrusion in which the displaced disk 
material has completely lost continuity with the parent 
disk. Sequestration may reside anterior or posterior to the 
PLL, or rarely may be intradural. Extruded disks, includ- 
ing sequestrations, can migrate either superiorly or infe- 
riorly from the level of the parent disk space. 

In a herniation, any combination of disk constituents - 
nucleus pulposus, cartilage, fragmented apophyseal bone, 
anulus - may be displaced. To describe the location of a 
herniated disk in the axial (horizontal) plane, several 
terms, which refer to “anatomic zones”, have been pro- 
posed as part of the standardized nomenclature (Fig. 1). 




Fig. la, b. Left foram- 
inal (or lateral) disk 
herniation. Axial (a) 
and parasagittal (b) 
T1 -weighted images 
of the lumbar spine 
demonstrate loss of 
the normal epidural fat 
signal in the left neur- 
al foramen at L4-5. 
The herniated disk ap- 
pears to be an extru- 
sion in the parasagittal 
image and is en- 
croaching on the exit- 
ing left L4 nerve root, 
which is located in su- 
perior portion of the 
neural foramen. Loss 
of disk space height at 
L4-5 is not evident on 
the parasagittal image 






176 



B.C. Bowen 



Moving from central to lateral for a left-sided herni- 
ated disk, the location would be identified as “central”, 
“left central”, “left subarticular”, “left foraminal”, or “left 
extraforaminal” (synonymous with “far lateral”). Of 
course, a large herniated disk may span more than one 
zone. In the sagittal (craniocaudal) plane, anatomic 
zones, which can be used to describe the extent of mi- 
gration, are loosely defined as the “disk level”, the “in- 
frapedicular level”, the “pedicular level”, or the “supra- 
pedicular level”. 

When lumbar herniated disks migrate either superior- 
ly or inferiorly, the migrated component is found pre- 
dominantly in either the left or right half of the anterior 
epidural space in 94% of cases. This lateralization is due 
to the presence of a collagenous, sagittal midline septum 
(adherent to the PLL and the vertebral body periosteum, 
yet potentially detachable) which divides the anterior 
epidural space opposite the vertebral body into a left and 
a right compartment [6]. There is no consensus in the lit- 
erature regarding the relative frequency of superior ver- 
sus inferior migration of lumbar herniated disks. 

The portion of an extruded disk extending beyond the 
vertebral endplates may or may not have high signal in- 
tensity on T2-weighted images compared with the inter- 
vertebral (parent) portion. For sequestered disk fragments 
(free fragments), some investigators have noted that ini- 
tial high signal intensity may decrease with time, perhaps 
as a result of water loss. It is important to remember that 
disk herniation may occur in the absence of significant 
degeneration. This is uncommon and tends to occur in 
young persons participating in strenuous activities, or as 
a result of trauma. 

In unoperated patients, enhancement of the margin of 
a herniated disk due to peridiskal scar may occasionally 
be observed on post-contrast T1 -weighted images, espe- 
cially when there is a sequestered fragment. A separate, 
but perhaps related, finding that has been reported is the 
abnormal enhancement of lumbosacral nerve roots in ap- 
proximately 5% of unoperated patients with low back 
pain or radiculopathy. In one study, the nerve root en- 
hancement was associated with disk herniation in the ma- 
jority of cases. There is no consensus, though, as to 
whether a correlation exists between the observed root 
enhancement and clinical radiculopathy, and investigators 
caution that nerve root enhancement may be mimicked 
by the normal enhancement of intramedullary veins in 
the lumbosacral region [7]. 

A herniation through a break in the vertebral body 
endplate is referred to as an intravertebral herniation and 
gives rise to a SchmorTs node (SN). Chronic SNs are 
asymptomatic and most frequently found in the thora- 
columbar region. The thin invaginated rim of the chronic 
SN has decreased signal intensity on all MR imaging se- 
quences. The surroimding vertebral body marrow may 
have variable signal but lacks the diffuse hyperintensity 
on T2-weighted images associated with edema. Acute 
SNs can be symptomatic, and they exhibit MRI evidence 
of diffuse marrow edema [8]. Indentation of the endplate 



may be focal or diffuse. Loss of height of the parent disk 
space is atypical for acute SNs. 

Spinal Stenosis, Spondylosis Deformans and 
Degenerative Facet Disease 

In addition to the changes in disk morphology described 
previously, disk degeneration is also implicated in the de- 
velopment of other structural and biomechanical abnor- 
malities: spinal stenosis, facet arthrosis, and malalign- 
ment-instability (e.g. spondylolisthesis). 

The presence of osteophytes arising from the vertebral 
body margins at the site of attachment of the anulus fi- 
brosus is generally referred to as spondylosis deformans. 
It has been considered the most common degenerative 
process of the spine, probably occurring secondary to de- 
generative disk disease with disruption of Sharpey’s 
fibers and increased stress on the vertebral body margins. 
Some investigators, though, suggest that spondylosis de- 
formans should be defined narrowly as anterior and lat- 
eral changes in vertebral body apophyses that may ac- 
company normal aging and occur in vertebra that are nor- 
mal or slightly decreased in height. This definition dis- 
tinguishes spondylosis from osteophyte formation occur- 
ring as part of intervertebral osteochondrosis, a degener- 
ative process involving the vertebral endplates, the nu- 
cleus pulposus, and the anulus fibrosus. In intervertebral 
osteochondrosis, disk space narrowing, vacuum phenom- 
enon, and vertebral endplate changes are observed. 

Degenerative disease (osteoarthritis) of the facet joints 
typically occurs in combination with degenerative disk 
disease. Synovial joints like the facet joints (and the cer- 
vical uncovertebral joints) are susceptible to the develop- 
ment of joint space narrowing, osteophyte formation, 
subchondral sclerosis, cyst formation, and subluxation. 
These degenerative changes affecting the nociceptors in 
the synovium and joint capsule, as well as nerve root im- 
pingement (in the neural foramen or lateral recess) from 
hypertrophied facets, may produce symptoms of pain and 
radiculopathy. Enlargement, buckling or redimdancy of 
the ligamentum flavum may be seen in association with 
degenerated, hypertrophied, and sclerotic facets. Juxta-ar- 
ticular (synovial, or rarely ganglion) cysts occur secon- 
darily and may compress the thecal sac or nerve roots, al- 
so resulting in pain, with or without radiculopathy. 

The findings that help to characterize intraspinal, juxta- 
articular cyst are its location (epidural, posterolateral), its 
apparent continuity with a hypointense, degenerated facet 
joint, and its hypointense rim on T2-weighted images. 
These cysts may have variable signal intensity depending 
on whether they contain synovial or other watery fluid, he- 
morrhage, proteinaceous material or air. The hypointensi- 
ty of the rim on T2-weighted images has been attributed to 
the presence of a fibrous capsule with hemosiderin de- 
posits or fine calcification. Post-contrast enhancement of 
the rim probably reflects the presence of inflammation, 
and may be usefiil to better define the lesion in suspected 




Degenerative Diseases of the Spine 



177 



cases. Hemorrhage into a cyst has been proposed as a 
mechanism to explain acute exacerbation of chronic low 
back pain. Conversely, spontaneous resolution of symp- 
toms has been attributed to decompression of the cyst in- 
to the adjacent facet joint as inflammation resolves. 

Lumbar Spinal Stenosis 

The bone proliferation and enlargement that accompany 
vertebral body marginal osteophj^e formation and facet 
degeneration frequently coexist and contribute, along 
with soft tissue changes, to degenerative spinal stenosis. 
In lumbar spinal stenosis, narrowing of the central spinal 
canal (central stenosis), lateral recesses, and neural formi- 
na may coexist or occur independently. Measurements of 
the dimensions of the bony canal for central stenosis are 
no longer recommended, because frequently they are not 
accurate predictors of clinical symptoms and because 
MRI provides better depiction of thecal sac narrowing 
due to degenerative osseous and soft tissue (e.g. ligamen- 
tous) changes. Obliteration of the epidural fat that ac- 
companies spinal stenosis is usually well shown on Tl- 
weighted MR images. In symptomatic patients with only 
mild degenerative disease, CT or MRI is useful to detect 
developmentally shortened pedicles that are associated 
with a narrowed canal, predisposing to symptoms (“con- 
genital stenosis”). 

The lateral recess is bordered posteriorly by the superi- 
or articular facet, laterally by the pedicle, and anteriorly by 
the vertebral body and disk. Lumbar lateral recess stenosis 
results when a hypertrophic superior facet encroaches on 
the the recess, often in combination with narrowing due to 
a bulging disk and osteophyte. Compression of the nerve 
root sleeve in the stenosed lateral recess can mimic a her- 
niated disk clinically. MRI is useful to differentiate lateral 
recess stenosis from central stenosis and to determine 
whether or not disk herniation is present. 

Foraminal stenosis occurs when a hypertrophic facet, 
vertebral body osteophyte, or bulging disk narrows the 
neural foramen and encroaches on the lumbar nerve roots, 
which are located in the superior portion of the foramen. 
Fortunately, degenerated disks first narrow the inferior por- 
tion of the foramen. When obliteration of the fat normally 
surroxmding the ventral nerve root and the dorsal root gan- 
glia in the foramen is detected on sagittal T1 -weighted im- 
ages, marked encroachment has occurred (Fig. 1). 

Cervical Spinal Stenosis 

In the cervical spine, central canal stenosis is usually sec- 
ondary to osteophytosis (spondylosis deformans) and liga- 
mentous thickening or redundancy (PLL and ligamentum 
flavum). Vertebral endplate changes, as described earlier, 
are often present. Osteophytic ridging and disk bulge or 
herniation may be inseparable on MRI and CT and thus are 
sometimes referred to as disk-osteophyte complex or chon- 



dro-osseous spur. Disk degeneration with loss of disk 
space height contributes to overriding and degeneration of 
the uncoverterbral joints. Hypertrophy of the uncinate 
processes and the facets as a result of imcovertebral joint 
and facet joint osteoarthritis produces foraminal stenosis, 
and the hypertrophied facets also contribute to the multi- 
factorial central canal stenosis. Symptoms of myelopathy, 
called cervical spondylotic myelopathy, develop as the cen- 
tral stenosis worsens; radiographic or CT measurements 
that are predictive for the diagnosis include: (i) decrease in 
the anteroposterior (AP) diameter of the canal (between C3 
and C7) from the normal value of approximately 17 mm to 
a value in the range from 10 to 14 mm (11 mm is fre- 
quently quoted), (ii) decrease in the ratio of the AP diam- 
eter of the canal to the AP vertebral body diameter from a 
value of 1 .0 or greater for a normal canal to a value of 0.8 
or less, and (iii) a cross-sectional area of the canal less than 
60 mm^. In the diagnosis of foraminal stenosis, CT has 
been favored, although two- or three-dimensional gradient 
recalled echo (GRE) MR images are increasingly being 
used to confirm clinical evidence of radiculopathy due to 
foraminal stenosis. MRI is the procedure of choice in as- 
sessing myelopathy because of the ability to detect abnor- 
malities in size, shape, and signal intensity of the cord. 
Patients who have abnormal signal intensity within the cer- 
vical cord tend to have more severe myelopathic symptoms 
and signs than patients with normal cord signal. Abnormal 
signal typically appears as hyperintensity on T2-weighted 
images and has been attributed to cord compression from 
the hypertrophic bony and ligamentous changes responsi- 
ble for central canal stenosis. The intramedullary hyperin- 
tensity results from any or all of the following pathologi- 
cal processes: edema, demyelination, gliosis and myelo- 
malacia. Edema is almost certainly a contributor to the hy- 
perintensity in cases where the abnormal signal intensity 
disappears or diminishes following surgery, as has been 
observed by several investigators. 

Ossification of the posterior longitudinal ligament 
(OPEL) generally produces severe central canal stenosis 
and significant myelopathy (Fig. 2). Patients typically 
present in the sixth decade with upper and lower extrem- 
ity weakness, dysesthesias, and neck pain. OPEL begins 
with calcification and progresses to frank ossification, 
first in the upper cervical spine and then later in the low- 
er cervical and upper thoracic spine. Four types of OPEL 
have been proposed on the basis of the CT appearance: 
(i) continuous, with OPEL extending confluently over 
multiple levels (27% of cases); (ii) segmental, with OPEL 
limited to the posterior margins of the vertebral bodies 
(39%); (iii) mixed continuous and segmental OPEL 
(29%); and (iv) OPEL crossing the disk space only (5%). 

CT and plain radiography are probably preferable to 
MRI in identifying subtle calcification and ossification, 
yet MRI is valuable for identifying cord compression. 
The ossified ligament may have fatty marrow and thus in- 
creased signal on T1 -weighted images. OPEL can be as- 
sociated with ligamentum flavum calcification and ossi- 
fication, and when combined, these processes may result 




178 



B.C. Bowen 




Fig. 2a-d. Cervical spondylosis with ossification of the posterior 
longitudinal ligament (OPLL). Sagittal T1 -weighted image (a) and 
fast spin echo T2-weighted image (b) reveal osteophytes or disk os- 
teophytes at each intervertebral disk space from C2-3 to C6-7, with 
cord compression at C4-5 and C5-6. The posterior longitudinal lig- 
ament appears to be thickened at several vertebral levels, including 
C5 where the axial gradient-echo MR image (c) and the axial CT 
image (d) demonstrate evidence of OPLL. Note the type 1 endplate 
changes at C3-4, and the loss of normal cervical lordotic curvature 



in circumferential compression of the cord. An associa- 
tion of OPLL with difflise idiopathic skeletal hyperosto- 
sis (DISH) has also been reported. 

An important finding on CT or MRI is the detection of 
calcification and ossification at the level of the vertebral 
body either segmentally or continuously over several lev- 
els. This helps to differentiate OPLL (95% of cases) from 
osteophytes and calcified herniated disks, which should 
be present at the level of the disk space only. For patients 
with myelopathy, surgical treatment is aimed at decom- 
pressing the cord. Both anterior and posterior approach- 
es are used. In the last decade, numerous studies have 
shown clinical benefits when multilevel disease is treat- 
ed with a canal-expansive laminoplasty procedure [9]. 
This procedure is usually done at each level from C3 to 
Cl, and then bone grafts are placed across the opening at 
alternate levels (usually C3, C5, and Cl) in order to keep 
the “door” open and the cord uncompressed. The same 
procedure has been used for many years to successfully 
treat multilevel cervical spondylotic myelopathy. 

Spondylolisthesis 

Spondylolisthesis, which is the most frequently observed 
example of malalignment, is defined as anterior slippage 
of a vertebra relative to the subjacent vertebra. The slip- 
page is graded on a scale of 1 to 4: one-fourth or less of 
the vertebral body width is grade 1, one-fourth to one- 
half is grade 2, one-half to three-fourths is grade 3, and 
three-fourths to the entire width is grade 4. Grade 1 ac- 
counts for more than 90% of cases. The two most com- 
mon causes are bilateral isthmic (pars interarticularis) de- 
fects, referred to as isthmic or spondylolytic spondylolis- 
thesis, and degenerative facet disease resulting in degen- 
erative spondylolisthesis. The pars abnormalities in isth- 
mic spondylolisthesis probably result from a combination 
of hereditary dysplasia of the pars and repeated stress 
fractures that result in persistent defects or healing with 
sclerosis and elongation of the isthmus. 

Spondylolisthesis is readily detected with MRI, using 
direct sagittal imaging, or with CT, using sagittal refor- 
matted images. The pars defects in spondylolysis, though, 
are more reliably demonstrated with CT and plain radi- 
ography. On MRI, evaluation of the pars is optimally 
done using T1 -weighted sagittal images. When the hy- 
perintense signal from marrow extends continuously 
from the superior articular process through the pars to the 
inferior articular process, then the pars is intact. 
Unfortunately, if signal abnormality or discontinuity is 
present in the pars region, the MRI findings are not spe- 
cific for a pars defect since they may be due to other eti- 
ologies such as partial volume averaging with a degener- 
ated facet, osteoblastic metastasis, or benign sclerosis. 
Spondylolisthesis is usually accompanied by bulging or 
“pseudobulging” of the disk. Elongation of the foramina 
due to vertebral slippage and foraminal encroachment by 
the bulging disk typically leads to compromise of the 




Degenerative Diseases of the Spine 



179 



nerve roots in the foramina. Disk herniation is less com- 
mon at the level of spondylolisthesis and more common 
at the level immediately above. 

Several congenital clefts of the neural arch have been 
described. From anterior to posterior along the neural 
arch, these include persistent neurocentral synchondrosis, 
retrosomatic cleft, retroisthmic cleft, and spina bifida. 
Retrosomatic and retroisthmic clefts are usually detected 
incidentally and should be distinguished from the pars 
(isthmic) defect in spondylolysis. The frequency of con- 
tralateral spondylolysis involving a vertebra with a 
retroisthmic cleft is many times greater than the preva- 
lence of spondylolysis in the general population. 

Postoperative Lumbar Spine 

Recurrent or residual low back pain in a patient after lum- 
bar disk surgery has a reported incidence of 5%-40%, and 
the syndrome has been called the “failed back” or “failed 
back surgery” syndrome (FBSS). Potential causes include 
epidural fibrosis (“scar”), recurrent or persistent disk her- 
niation, arachnoiditis, spondylolisthesis, and residual 
bony stenosis. Ross [10] demonstrated a significant asso- 
ciation between the presence of extensive peridural scar 
and the occurrence of recurrent radicular pain. 

Typically, a physician who is caring for a patient with 
symptoms of FBSS wants to know if the clinical symp- 
toms (recurrent back pain, radiculopathy, and functional 
incapacitation) are primarily due to scar or disk. The re- 
ported accuracy of post-contrast MRI in distinguishing 
between scar and disk in patients at least 6 weeks after 
surgery is 96%-100%. Whether the time elapsed since 
surgery is months or years, scar consistently enhances on 
images acquired immediately following injection of con- 
trast material. Because it is avascular, the disk does not 
enhance on these early images (Fig. 3). On delayed im- 
ages (>30 min following injection), disk material may 
enhance because of diffusion of the low molecular 
weight contrast material (gadolinium chelate) into the 
disk from adjacent scar, especially when there is a rela- 
tively large volume of scar compared to the volume of 
herniation. A secondary sign that favors scar over recur- 
rent or persistent disk is retraction of the thecal sac to- 
ward the region of aberrant epidural soft tissue. The 
presence of mass effect is not helpful since both epidur- 
al scar and disk can produce this finding. The addition 
of a frequency-selective fat-saturated pulse sequence to 
the routine post-contrast T1 -weighted images has been 
found to improve visualization of enhancing scar, help 
distinguish scar from recurrent herniated disk, and more 
clearly show the relationship of scar to nerve roots and 
thecal sac. 

Lumbar arachnoiditis, which has been cited as a cause 
of FBSS in up to 16% of cases, can have a variable ap- 
pearance and has been categorized into three groups or 
patterns. These patterns, which may overlap, can be ob- 
served with myelography, CT myelography, or MRI, and 




Fig. 3a, b. Postoperative, recurrent lumbar disk herniation. Axial 
T2-weighted (a) and post-contrast T1 -weighted (b) images at the 
L4-5 level show thinning and disruption of the left ligamentum 
flavum, consistent with a previous left partial laminectomy. On the 
T2-weighted image, the soft tissue mass in the left side of the canal 
could be scar or recurrent disk herniation. On the post-contrast Tl- 
weighted image, the bulk of the mass does not enhance, which is 
consistent with recurrent disk herniation. The thin rim of enhance- 
ment bordering the mass represents mild adjacent scarring 



differ from the normal feathery appearance of the nerve 
roots surrounded by fluid. Pattern 1 is clumping of nerve 
roots into cords and represents central adhesion of the 
roots within the thecal sac. Pattern 2 is referred to as the 
“empty thecal sac” sign and represents adhesion of the 



180 



B.C. Bowen 



nerve roots to the meninges. In pattern 3, the thecal sac 
is filled by a mass, representing the end-stage of the in- 
flammatory response. On myelography, this appears as a 
block with an irregular “candle-dripping” appearance, 
whereas CT myelography and MRI show only a non-spe- 
cific soft tissue mass. Arachnoiditis may or may not show 
enhancement on post-contrast T1 -weighted images, and 
the diagnosis is best made on the basis of the morpholo- 
gy of the roots and sac. 

References 

1. Bowen BC (2001) Spine imaging: case review. Mosby, 
Philadelphia 

2. Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N 
(2001) Magnetic resonance classification of lumbar interver- 
tebral disc degeneration. Spine 26:1873-1878 

3. Tanaka N, An HS, Lim TH, Fujiwara A, Jeon CH, Haughton 
VM (2001) The relationship between disc degeneration and 
flexibility of the lumbar spine. Spine J 1:47-56 

4. Czervionke LF, Haughton VM (2002) Degenerative disease of 



the spine. In: Atlas SW (ed) Magnetic resonance imaging of 
the brain and spine, 3rd edn. Lippincott Williams Wilkins, 
Philadelphia, pp 1633-1713 

5. Fardon DE, Milette PC (2001) Nomenclature and classifica- 
tion of lumbar disc pathology: recommendations of the com- 
bined task forces of the North American Spine Society, 
American Society of Spine Radiology, and American Society 
of Neuroradiology. Spine 26:E93-E113 

6. Schellinger D, Manz HJ, Vidic B, Patronas NJ, Deveikis JP, 
Muraki AS, Abdullah DC (1990) Disk fragment migration. 
Radiology 175:831-836 

7. Lane JI, Koeller KK, Atkinson LD (1994) Enhanced lumbar 
nerve roots in the spine without prior surgery: radiculitis or 
radicular veins? AJNR Am J Neuroradiol 15:1317-1325 

8. Wagner AL, Murtagh FR, Arrington JA, Stallworth D (2000) 
Relationship of Schmorl’s nodes to vertebral body endplate 
fractures and acute endplate disk extrusions. AJNR Am J 
Neuroradiol 2 1 :276-28 1 

9. Lee TT, Manzano GR, Green BA (1997) Modified open-door 
cervical expansive laminoplasty for spondylotic myelopathy: 
operative technique, outcome, and predictors for gait improve- 
ment. J Neurosurg 86:64-68 

10. Ross JS (1999) MR imaging of the postoperative lumbar spine. 
Magn Reson Imaging Clin N Am 7:513-524 




IDKD 2004 



Degenerative Diseases and Pain Syndromes 

XL. Drape 

CHU Cochin, Radiology Service B, Paris, France 



Introduction 

Degenerative disease of the lumbar spine is very com- 
mon, affecting two-thirds of adults during their life- 
times. It represents a real public health challenge due to 
costs resulting in lost days of work and a high rate of in- 
validity. 

Imaging modalities may demonstrate physiological 
mechanisms of low back pain as well as radiculalgia and 
allow adequate therapy to be administered. Radioclinical 
correlation is mandatory due to the high rate of abnormal 
findings demonstrated even in asymptomatic patients. 
This presentation is not exhaustive but discusses particu- 
lar points concerning diskopathies (erosive or calcifying), 
annular tears, Schmorl’s nodes, C1-C2 osteoarthritis and 
lumbar spine stenosis. 

Erosive Disk Disease 

Common degenerative disk disease (DDD) is usually eas- 
ily diagnosed. Nevertheless, DDD may be erosive in 
some cases, resulting in inflammatory type pain, and may 
be confused with infectious diskitis. These erosive disk 
diseases (EDDs) may cause disk lysis (loss of 50% of 
disk height in less than two years) or vertebral instability 
[1]. Erosions of vertebral endplates, with disk space nar- 
rowing on plain films or abnormal signal intensity of disk 
or vertebral endplates on magnetic resonance imaging 
(MRI), are suggestive of spondylodiskitis [2]. 

Lumbar spine involvement and higher frequency in 
males are common in both DDD and EDD. In case of 
multiple EDD, calcium pyrophosphate deposition disease 
(CPPD) must be suspected. 

On plain radiography and computed tomography (CT), 
four signs suggest EDD [3]; 

- Small erosions with peripheral sclerosis and well-de- 
fined margins, 

- Osteosclerosis of adjacent vertebral endplates, anteri- 
or in location, with large, well-defined dome-shaped 
limits, 

- “Excentered” osteophytes suggestive of instability [4], 



- Intradiskal gas [5] phenomenon that may be better 
demonstrated on stress view in hyperextension. 

On MRI examination, disk and vertebral endplates 
demonstrate low signal intensity on T2-weighted images, 
although areas of high signal intensity may be present in 
case of intradiskal gas bubbles secondarily filled with 
fluid in decubitus [6]. Linear or focal contrast enhance- 
ment of vertebral endplates suggests lesions of annulus or 
vertebra [7]. Displacement of the common vertebral lig- 
ament by osteophytes must not be confused with abscess. 
Edematous signal intensity (Modic 1) of the vertebral 
endplates is poorly suggestive. These modifications occur 
in 4% of DDD but in 100% of EDD [8]. An area of fat- 
ty infiltration (Modic 2) commonly surrounds these areas 
of low signal intensity on T1 -weighted images. Evolution 
of Modic 1 into Modic 2 is possible. 

In rare cases, imaging does not allow diagnosis and 
percutaneous bone, and disk biopsies are mandatory. 

Idiopathic Calcifying Disk Disease 

Disk calcification, a common and incidental finding, is 
idiopathic in origin [9]. In children, calcification is com- 
monly seen in cervical spine. In adults, it is more com- 
mon in thoracic and lumbar spines. Cadaveric correla- 
tions in elderly people demonstrated calcifications of the 
annulus fibrosus in 71% of cases [10]. 

Symptomatic calcifications are usually central in loca- 
tion and suggestive of apatite depositions. Thinner and 
peripheral calcifications are more suggestive of CPPD. 

Clinical findings are variable and include asympto- 
matic manifestations and central cord compression due to 
large thoracic calcified disk herniation. Inflammatory 
type pain may simulate diskitis. Linear calcifications may 
suggest calcified disk herniation with associated fissure 
of the annulus. As in calcified tendinitis, calcification 
may disappear following pain manifestation. 

During the inflammatory phase, uptake on bone scans 
is common in disk as well as in vertebral bodies. Signal 
hyperintensity on T1 -weighted images, close to the calci- 
fication, may be seen [11]. 




182 



J.L. Drape 



Painful Disk without Herniation 

The diskoradicular impingement by herniated disk is the 
commonest etiology of lumboradiculalgia. The acute 
compression of a normal peripheral nerve is usually pain- 
less but accompanied by dysesthesiae. The radicular suf- 
fering may be mechanical but also secondary to inflam- 
matory, chemical or scarring reactions or disturbed mi- 
crovascularization. Some pains of the lower limbs associ- 
ated with low back pain may be not situated along a der- 
matoma; therefore the term “radiculopathy” is used [12], 
These atypical pains are often associated with disk ab- 
normalities without diskoradicular impingement. 
Imaging may reveal intradiskal tears. 

Three types of CT abnormalities may be evocative of 
disk tear: 

- Disk hypodensity. Normally the disk is homogeneous 
with a density (80 HU) greater than that of muscle. 
Posterior peripheral hypodensity may be observed at a 
median or paramedian location. This hypodensity may 
be more or less extensive. It is usually associated with 
a small disk irregularity, without a true herniation. 

- Irregularities or notch of the inferior or superior verte- 
bral plates. The defect of the listel of the vertebral 
plate is more or less regular, concave, and median or 
paramedian. It is evocative of an avulsion of the pe- 
ripheral fibers of the annulus and may favor the devel- 
opment of a true herniation. 

- Soft tissue abnormalities in front of the defect of the 
vertebral plate. The association of a small convex area 
of intermediate or disk density surrounding the defect 
is in favor of an annular abnormality. Some small iso- 
or hyperdense areas at the periphery of the disk may 
be due to inflammatory reaction or disk microffag- 
ments. 

On MRI, diffuse low signal intensity of the disk is sug- 
gestive of DDD. Peripheral areas of the disk as well as the 
posterior common vertebral ligament must be carefully 
studied. Focal signal abnormalities (high T2 focus or con- 
trast enhancement) may be noted. Fast T1 -weighted spin 
echo sequences are sensitive. Clinical significance of 
these abnormalities is debated since they may be present 
in asymptomatic patients [13]. In contrast, obvious signal 
abnormalities on T2-weighted images may correspond to 
annular tear demonstrated by diskography or diskoCT 
[14]. 

Spreading, linear or oval-shaped, peripheral signal ab- 
normalities are suggestive of causal disk , particularly in 
association with abnormalities of the bone-annulus junc- 
tion. 



Schmorl’s Nodes 

Schmorl’s nodes (SN) are commonly found in cadaveric 
studies and are frequently seen on MRI in asymptomatic 
patients [15]. Less than one-third of SN are demonstrat- 
ed by plain films. Plain film sensitivity depends on node 



size and surrounding adjacent bony osteosclerosis. Large 
nodes are commonly symptomatic. They must not be 
confused with a tumoral or infectious process. They are 
idiopathic in origin or secondary to axial stress. Repair 
mechanisms are possible with secondary ossification; in- 
cidence declines with age [16]. 

The nature of Schmorl's nodes is variable and includes 
cartilage matrix, fibrous scary tissue and peripheral vas- 
cular proliferation. MRI demonstrates vascularized nodes 
following gadolinium infusion. Enhancement is more 
suggestive of repair phenomenon than symptomatic node. 
Associated edematous manifestations of vertebral end- 
plates (similar to Modic 1 in DDD) are noted in one-third 
of enhancing nodes and are more common when symp- 
tomatic [15]. 

C1-C2 Osteoarthritis 

C1-C2 osteoarthritis (C1-C2 OA) may cause obstinate 
cervical or occipital pain. It is responsible for unilateral 
cervical or occipital pain, head ache and retroauricular 
pain [17], and usually occurs in aged women with multi- 
ple osteoarthritic locations. Limitation of rotation is fre- 
quent. Only 4 % of patients with peripheral OA present 
C1-C2 OA. 

Diagnosis is made on the open mouth view. Lateral or 
rotating instabilities of C1-C2 result from severe asjmi- 
metric cartilage narrowing. Most often, lesions are uni- 
lateral in location, at the right side, better demonstrated 
by volumic CT with multiplanar reconstructions. 

MRI may be confusing, demonstrating bone edema or 
synovial proliferation. Medical treatment includes C1-C2 
block with steroid administration by a posterior or later- 
al approach. 

Atlanto-odontoid osteoarthritis is more frequent than 
lateral C1-C2 OA. Symptoms include occipital pain [18]. 
Lateral view is more informative than the open mouth 
view due to multiple superimpositions (e.g. styloids, 
mandible). 

On the anteroposterior view, osteophytes of the supe- 
rior and lateral aspects of C 1 result in a horseshoe calci- 
fication mimicking CPPD. Lateral view may emphasize 
lesions [19]. Volumic CT remains the best modality to 
demonstrate C1-C2 OA. Joint space narrowing, articular 
gas bubbles, ostephytes and periarticular ossifications are 
common, as are transverse ligament calcifications. Direct 
intra-articular steroid administration is uncommon and 
rather difficult due to the dangerous anatomic relation- 
ship. Lateral C1-C2 steroid administration remains possi- 
ble but communication with atlanto-odontoid joint occurs 
only in 20% of cases [20]. 

Lumbar Spine Stenosis and MR Myelography 

Degenerative lumbar spine stenosis (DLSS) is common 
in elderly people. Stenosis may be central or lateral in lo- 




Degenerative Diseases and Pain Syndromes 



183 



cation due to osseous or ligamental hypertrophy. Usually, 
stenosis involves multiple levels and is symmetrieal. 
Plain films, CT and myelography are eommonly used 
techniques but may emphasize lesions. 

The value of routine MR myelography remains poor 
(6%) exeept for evaluation of DLSS [21]. Three-dimen- 
sional (3D) myelographic sequenees with maximum in- 
tensity projection (MIP) reformations or ultrafast thick 
single slices are informative about the degree of stenosis 
as well as effusions in facet joints [22]. Facet joint effu- 
sion is eommon in OA. It results from aetive OA but not 
always at the most severely involved level. Synovial eyst 
may occur, causing nerve root impingement. 

Communieation between facet joints at the same level 
may be present through the interspinous bursa. This eom- 
munication is seen by faeet joint arthrography [23]. 
Interspinous bursitis may be symptomatic (Baastrup's 
disease or kissing spine). 

Plain films demonstrate faeet joint OA, DDD causing 
disk space narrowing and bony remodeling of large spin- 
ous processes particularly at the L4-L5 level [24]. Only 
MRI directly demonstrates interspinous bursitis that may 
be inflammatory or ealcified. Steroid administration is 
possible during bursography, which may also demon- 
strate communieation with facet joints or intracanalar di- 
vertieulae. 



References 

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copathie destructrice rapide. In: Morvan G, Deburge A, Bard 
H, Laredo JD (eds) Le rachis lombaire degeneratif Sauramps 
Medical, Montpellier, pp 279-283 

2. Stoller DW, Steinkirchner TM, Porter BA (1997) The spine. In: 
Stoller DW (ed) Magnetic resonance imaging in orthopaedics 
and sports medicine, 2nd end. Lippincott Williams Wilkins, 
Philadelphia, pp 1059-1162 

3. Modic MT, Masaryk TJ, Ross JS (1988) Imaging of degener- 
ative disk disease. Radiology 168:177 

4. McNab I (1971) The traction spur. An indicator of segmental 
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5. Larde D, Mathieu D, Frija J (1982) Spinal vacuum phenome- 
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6. Malghem J, Maldague B, Labaisse MA (1993) Intervertebral 
vacuum cleft: changes in content after supine positioning. 
Radiology 187:483 



7. Stabler A, Weiss M, Scheidler J (1996) Degenerative disk vas- 
cularisation on MRI: correlation with clinical and histopatho- 
logic findings. Skeletal Radiol 25:119-126 

8. Modic MT, Steinberg PM, Ross JS (1988) Degenerative disk 
disease: asssessment of changes in vertebral body marrow 
with MR imaging. Radiology 166:193 

9. Ballou SP, Khan MA, Kushner I (1977) Diffuse intervertebral 
disc calcification in primary amyloidosis. Ann Intern Med 
85:616-617 

10. Weinberger A, Myers AR (1978) Intervertebral disc calcifica- 
tion in adults: a review. Semin Arthritis Rheum 1:69-75 

11. Bangert BA, Modic MT, Ross JS, Obuchowski NA, Perl PJ, 
Ruggieri PM, Masaryk TJ (1995) Hyperintense disks on Tl- 
weighted MR images: correlation with calcification. 
Radiology 195:437-443 

12. Millette PC (1994) Radiculopathy, radicuar pain, radiating 
pain, referred pain: what are we really talking about? 
Radiology 192:281-282 

13. Stadnik TW, Lee RR, Coen HL, Neirynck EC, Buisseret TS, 
Osteaux MJL (1998) Annular tears and disk herniation: preva- 
lence and contrast enhancement on MR images in the absence 
of low back pain or sciatica. Radiology 206:49-55 

14. Schellhas KP, Pollei SR, Gundry CR, Heithoff KB (1996) 
Lumbar disc high intensity zone: correlation of magnetic res- 
onance imaging and discography. Spine 21:79-80 

15. Stabler A, Bellan M, Weiss M, Gartner C, Brossmann J, Reiser 
MF (1997) MR imaging of enhancing intraosseous disk herni- 
ation (SchmorTs nodes). AJR Am J Roentgenol 168:933-938 

16. Hamanishi C, Kawabata T, Yosii T, Tanaka S (1994) SchmorTs 
nodes on magnetic resonance imaging: their incidence and 
clinical relevance. Spine 19:450-453 

17. Ehni G, Benner B (1984) Occipital neuralgia and the C1-C2 
arthrosis syndrome. J Neurosurg 61:961-965 

18. Zapletal J, Hekster RE, Straver JS, Wilmink JT, Hermans J 
(1996) Relationship between atlanto-odontoid osteoarthritis and 
idiopathic suboccipital neck pain. Neuroradiology 38:62-65 

19. Zapletal J, Hekster RE, Wilmink JT, Hermans J, Mallens WM 
(1995) Atlanto-odontoid osteoarthritis: comparison of lateral 
cervical projection and CT. Eur Spine 4: 238-241 

20. Chevrot A, Cermakova E, Vallee C, Chancelier MD, Chemla 
N, Rousselin B, Langer-Cherbit A (1995) C1-C2 arthrography. 
Skeletal Radiol 24:425-429 

21. O’Connell MJ, Ryan M, Powell, T, Eustace S (2003) The val- 
ue of routine MR myelography at MRI of the lumbar spine. 
Acta Radiol 44:665-672 

22. Nagayama M, Watanabe Y, Okumura A, Amoh Y, Nakashita S, 
Dodo Y (2002) High-resolution single-slice MR myelography. 
AJR Am J Roentgenol 179:515-521 

23. Sarazin L, Chevrot A, Pessis E, Minoui A, Drape JL, Chemla 
N, Godefroy D (1999) Lumbar facet joint arthrography with 
the posterior approach. Radiographics 19:93-104 

24. Bywaters EG, Evans S (1982) The lumbar interspinous bursae 
and Baastrup’s syndrome. An autopsy study. Rheumatol Int 
2:87-96 




IDKD 2004 



Neoplastic Spinal Cord Disease 

D.L. Baleriaux 

Neuroradiology Clinic, Department of Radiology, Erasme University Hospital, Free University of Brussels, Brussels, Belgium 



Introduction 

Spinal cord tumors are rare. Every radiologist should 
be able to recognize and readily identify those lesions 
often found in younger patients or children. Early di- 
agnosis plays an important role in the management of 
the lesions and will interfere with the prognosis and fi- 
nal outcome of the patient. Clinical symptoms of cord 
tumors are usually of insidious onset: pain may be for 
long the only complaint while motor deficits often ap- 
pear later. Before the advent of magnetic resonance 
imaging (MRI), the diagnosis of a spinal cord tumor 
was often delayed. It is important, however, to diagnose 
those tumors at an early stage as new, efficient, surgi- 
cal techniques including the use of Cavitron ultrasound 
aspiration (CUSA) may heal the patient or at least stop 
tumor evolution. Adequate management by using the 
proper diagnostic tools and careful analysis of the MR 
images help describe important features such as solid 
nodule, cystic components, associated hydrosy- 
ringomyelia and guide the surgeon. On the other hand, 
intramedullary lesions with mass effect may mimic 
spinal cord neoplasm: differential diagnosis is essential 
to avoid unnecessary surgery and to plan and guide ad- 
equate biopsy if required. 

Examination Techniques 

Plain Radiography 

Standard X-ray films provide poor if no information at 
all concerning the intraspinal content. Still, mainly in 
young children and infants, a slow-growing in- 
tramedullary tumor may enlarge the spinal canal. The 
lower thoracic canal is often expanded in cases of a 
myxopapillary ependymoma of the conus. In the litera- 
ture, scoliosis is classically mentioned as being present 
in cases of intracanalar intramedullary tumors: any 
evolving scoliosis should at least raise the question of 
a possible underlying tumor. Spinal deformity is re- 
ported to occur in 46% of pediatric spinal cord neo- 



plasms. Torticolis or even a permanent “stiff neck” 
should also alert the radiologist and prompt a neuro- 
logical examination with, if necessary, an immediate 
MRI examination. Loss of the normal cervical lordosis 
detected on a sagittal plain film should prompt further 
investigate into the origin of the major pain presented 
by the patient. 

Computed Tomography 

The intracanalar content is increasingly visible with the 
recently developed computed tomography (CT) proto- 
cols. Still, subtle cord enlargement, small cystic compo- 
nents and spinal root anomalies are not easily detected 
with CT. Calcifications are rare in intramedullary tumors. 
For those reasons, I recommend not wasting time with 
plain spinal CT and suggest performing MRI immediate- 
ly. If MRI is not readily available, CT combined with in- 
trathecal contrast medium injection (myelo-CT) is a good 
alternative examination. Still, one should be aware that 
neurological worsening of the patient’s status may occur 
following lumbar puncture in cases of large in- 
tramedullary tumors. 

Myelography 

This has been the standard imaging procedure used for 
the diagnosis of intraspinal pathology. Still, it provides 
only an “indirect” approach, showing the contours and 
shape of the cord without the inner structure. Moreover, 
in case of myelographic “block”, only the inferior (when 
the injection is made by lumbar route) or superior (with 
suboccipital injection) limits of the tumor infiltration 
can be assessed. Myelo-CT is a useful complementary 
examination, as CT is more sensitive and usually allows 
determining both limits of the tumor. Myelo-CT also al- 
lows progressive or delayed enhancement of in- 
tramedullary cavities. Today, both myelography and 
myelo-CT should still be used by radiologists for the rare 
cases of patients excluded from MRI, but the techniques 
should definitely be abandoned in favor of MRI when- 
ever possible. 




185 



Neoplastic Spinal Cord Disease 

Magnetic Resonance Imaging 

MRI examination of the spine must systematically in- 
clude the use of at least two different imaging planes 
(usually sagittal and axial), two different imaging tech- 
niques (Tl- and T2-weighted imaging) and gadolinium- 
enhanced T1 -weighted images. MRI shows not only the 
shape of the cord (external contours) but also the internal 
changes within the cord. I recommend that every signal 
behavior anomaly as well as every change in shape and 
morphology of the cord be systematically described to 
answer some fundamental questions: 

- Is the lesion a neoplasm or an inflammatory or infec- 
tious mass? 

- Is the lesion intra- or extramedullary? 

- If the lesion is a neoplasm, where is the solid neoplas- 
tic infiltration? Can the tumor limits be described with 
confidence? Are the borders well defined? 

- If there are cystic components, are they intratumoral or 
extratumoral, the so-called associated cysts due to en- 
largement of the ependymal canal? 

- How do these components change after gadolinium in- 
jection? Indeed, the borders of a “satellite” or associ- 
ated cyst do not enhance, contrary to those of a tu- 
moral cyst. 

Secondary dilatation of the ependymal canal (hy- 
dromyelia) is often associated with spinal cord tumors: 
at the CO-Cl level we sometimes observe a focal, more 
important enlargement of the ependymal canal that we 
call a “bulbar cyst” (Fig. 1). In fact, a syrinx is more 
likely to be found above (49%) than below (1 1%) the tu- 
mor level. In 40% of cases, a syrinx can be identified 
above and below a tumor. Ependymoma and heman- 
gioblastoma are the most common tumors to be associ- 
ated with syringes. 



Fig. 1. Various 
components and 
anomalies identi- 
fied on an MR im- 
age in cases of in- 
tramedullary tu- 
moral lesions. (Re- 
produced with per- 
mission from MRI 
of Spinal Cord Le- 
sions, an educa- 
tional CD-ROM. 
Lasion, Aartselaar, 
Belgium) 




bulbar cyst 
hydromyelja 
- satellite cyst 

intratumoral cyst 
solid nodule 



- satellite cyst 



• hydromyelia 



MR Myelography 

This technique provides heavily T2-weighted images 
simulating typical myelographic images. This noninva- 
sive and elegant technique shows nicely not only the 
spinal roots but also the vascular structures on the sur- 
face of the cord. It helps to define the intramedullary 
cyst-like cavities. 

Spinal Angiography and MR Angiography 

“Conventional” digital angiography is rarely performed 
for intramedullary tumors. Nevertheless, it should be 
performed whenever a true arteriovenous malformation 
is suspected on the basis of standard MR images or in 
the rare cases in which it is mandatory to know exactly 
where the artery of Adamkiewicz originates. Nowadays, 
MR angiography is available but spatial resolution is 
usually not sufficient to be able to study spinal vessels 
of small caliber. 



Spinal Cord Neoplasms 

Tumors of the spinal cord are rare. In a general hospital, 
only 5% of spinal tumors are intramedullary, while 40% 
are intradural extramedullary and 55% are extradural. 
Astrocytoma, ependymoma and hemangioblastoma are 
the most frequent tumors: they should be recognized pre- 
operatively because surgical management as well as prog- 
nosis vary according to tumor histology. 

In adults, ependymomas represent 60% of all in- 
tramedullary tumors. Astrocytomas account for about 
30% of spinal cord gliomas. Hemangioblastomas are less 
frequent and represent 5%. Clinical presentation is poor- 
ly specific; pain is the most common finding and usual- 
ly the first symptom to be reported. Sensory and motor 
deficits are variable and occur in function of tumor lo- 
calization. Urinary disturbances and impotence are rare 
and appear late in the clinical course of the disease: they 
occur usually coincident with motor paralysis of the legs. 

In children, astrocytoma is far the most frequent in- 
tramedullary neoplasm. In fact, my colleagues and I have 
never observed a case of ependymoma in a child, and the 
cases reported in the literature are few. In children, pain 
is equally the most frequent symptom, reported in 42% 
of cases. Motor regression is present in 36%, gait abnor- 
mality in 27%, torticolis in 27% and progressive 
kyphoscoliosis in 24% of cases; 89% are low-grade le- 
sions. 

Astrocytoma, even in adults, is mostly encountered in 
younger patients (mean age in our series, 29 years) 
with a predominance of males (63%). Astrocytomas 
involve mostly large portions of the cord and fre- 
quently harbor cystic components. Satellite cysts and 
secondary hydromyelia can also be observed. 
Associated edema is often moderate and contrast en- 
hancement is relatively mild and heterogeneous. 




186 



D.L. Baleriaux 



Astrocytomas are found more often in the thoracic 
spine but may occupy any part of the cord. Seventy- 
five percent of astrocytomas are of low grade and 
progress slowly, while 25% are aggressive and high 
grade. An astrocytoma is usually eccentrically located 
and exhibits heterogeneous, moderate, and partial con- 
trast enhancement after gadolinium injection. 
Astrocytoma borders are frequently ill defined. 
Ependymomas are usually smaller and are preferentially 
located in the cervical or cervicothoracic spine. They 
originate from ependymal cells lining the ependymal 
canal and therefore are typically centered in the middle 
of the cord. Most are benign although malignant types 
may occur. They often show associated satellite or bulbar 
cysts. The enhancement after gadolinium administration 
is usually more homogeneous and intense compared to 
that of astrocytoma. Tumor borders are usually well de- 
fined. Moreover, a rather specific “cap sign” is often 
found in ependymomas: it corresponds to the presence of 
hypointense areas, capping both ends of the tumor. This 
sign is best seen on gradient echo images as it is in fact 
due to deposits of hemosiderin, the result of frequent 
chronic bleeding in ependymoma. Still, intratumoral he- 
morrhage may also occur in astrocytomas, explaining the 
sudden worsening of the neurological deficits. Recent 
bleeding is shown as hyperintense areas on T1 -weighted 
images. In my experience, gross total removal is possible 
in 70% of cases of ependymoma, in comparison to 33% 
of astrocytomas. 

Hemangioblastomas are richly vascularized tumors, usu- 
ally located sub-pially. They have two typical presenta- 
tions: either as a small tumoral nodule associated with ex- 
tensive edema, or as a small nodular tumor associated 
with an extensive cystic, often polylobulated cavity. The 
nodule always enhances strongly after gadolinium injec- 
tion. These tumors can be either solitary or multiple (if 
associated with von Hippel-Lindau disease). 

An intramedullary lymphoma may occur as part of a mul- 
tifocal lymphoma, with cerebral, cerebellar or brain stem 
lesions associated with the intramedullary lesion. 
Primary intramedullary lymphoma is rare. 

Spinal cord metastases are reported to be rare: in my ex- 
perience, however, they are easier to diagnose and occur 
probably more frequently than reported in the literature. 
Still, it is difficult to ascertain the true incidence of spinal 
cord metastases, as the clinical picture often is atypical 
and the lesions are seen in terminally ill patients. Autopsy 
is also biased, as the cord is often not systematically ex- 
amined. On the other hand, 2.4% of metastases removed 
surgically from the central nervous system (CNS) are lo- 
cated in the cord. Clinical symptoms are often non-spe- 
cific, but usually involve root pain. Today, the exquisite 
sensitivity of MRI enables intramedullary metastases to 
be easily detected. No specific MRI characteristics are 
seen. Usually they are small, nodular, well-defined le- 
sions that are hypointense on T2-weighted images. The 
enhancement pattern may be either ring-like or homoge- 
neous and intense. It is rare that a primary cancer is dis- 



covered by the identification of a solitary intramedullary 
metastasis. 

Gangliogliomas are rare tumors, representing 3.8% of all 
CNS tumors. They involve the upper cervical cord in the 
great majority of cases. One-third of gangliogliomas are 
seen in children, where spinal cord involvement (1.7%) is 
greater than cerebral (1.4%) or cerebellar (0.7%) in- 
volvement. 

Oligodendrogliomas are rare in the spinal cord. They 
exhibit no specific MRI characteristics. However, the 
few cases in my experience were relatively small tumors 
(involving two vertebral segments), with ill-defined 
borders and slight hyperintensity on T1 -weighted im- 
ages. No peritumoral edema or contrast enhancement 
was seen. 

Lipomas are relatively rare spinal cord tumors, represent- 
ing 6% of intramedullary tumors in our series. True in- 
tramedullary lipoma must be differentiated from cauda 
equina lipomas or lipomas associated with dysraphism, 
since the clinical, radiological, and surgical issues raised 
by these lesions are totally different. Although these tu- 
mors appear well-defined on MRI, often no cleavage 
plane from the surrounding spinal cord is found at 
surgery. Therefore, the tumor usually cannot be com- 
pletely resected without causing severe neurological 
damage. The typical hyperintensity of lipomas on Tl- 
weighted images makes these lesions easy to diagnose 
with MRI. 

Cavernomas are vascular malformations that may remain 
clinically silent for a long period of time. Often they are 
responsible for an acute or rapidly progressive medullary 
neurological deficit. Cavernomas represent 2.4% of all 
intramedullary tumors. All cases present with hemor- 
rhage. Before the advent of MRI, these lesions were ex- 
tremely difficult to diagnose, especially in the spinal 
cord, as they usually are small and do not enlarge the 
spinal cord. On the other hand, on MRI, intramedullary 
cavernomas (or cavernous hemangiomas) are usually eas- 
ily recognized. A reticulated appearance with areas of 
mixed signal intensity on both Tl- and T2- or T2*- 
weighted images is the most common finding. A promi- 
nent rim of decreased signal intensity is less commonly 
seen than in the brain. Contrast enhancement may occur. 
As cavernomas may be multiple, I recommend cerebral 
MRI whenever the diagnosis of cavernoma is suspected. 
If multiple, similar lesions are found in the brain, this 
should support a final diagnosis of cavernoma of the 
spinal cord. 

Schwannomas originate from Schwann cells and are 
always located on the posterior nerve root. This ex- 
plains why schwannomas classically are ex- 
tramedullary and are responsible for spinal cord com- 
pression. Less frequently they may be both extra- and 
intramedullary. In rare instances, they may be strictly 
intramedullary. Pure intramedullary schwannomas are 
well-defined, isointense lesions on Tl - and T2-weight- 
ed images with homogeneous enhancement after 
gadolinium injection. 




Neoplastic Spinal Cord Disease 

Differential Diagnosis 

Numerous non-neoplastic intramedullary lesions may 
simulate tumor infiltration and should be diagnosed 
properly in order to avoid unnecessary biopsy. Typically, 
those lesions include multiple sclerosis (MS) plaques, in- 
flammatory lesions, granulomas, and abscesses. 
Sarcoidosis is rare in the spinal cord. Diagnosis of an in- 
tramedullary lesion is facilitated when the patient has 
known systemic sarcoidosis. We observed two cases in 
which the patients had solitary spinal cord lesions pre- 
senting as intramedullary tumors. MRI demonstrated 
non-specific findings of a nodular lesion that strongly en- 
hanced on gadolinium-enhanced T1 -weighted images. 
Sarcoidosis should thus be included in the differential di- 
agnosis of a nodular lesion. Biopsy may be required and 
should be performed to establish the diagnosis when no 
systemic signs of sarcoidosis are known. 

Important concepts have to be kept in mind: every tu- 
mor does not necessarily enhance and conversely every 
enhancing mass is not a tumor. Extensive mass lesions, 
on the contrary, are most likely to be neoplasms. 

Conclusions 

MRI is the optimal imaging modality for the diagnosis of 
intramedullary neoplasms. The radiologist has an impor- 
tant role to play in carefully identifying and describing the 
lesion as well as suggesting the proper histological analy- 
sis for appropriate management and surgical treatment. 

Suggested Reading 

Baleriaux D, Parizel P, Bank WO (1992) Intraspinal and in- 
tramedullary pathology. In: Manelfe C (ed) Imaging of the 
spine and spinal cord. Raven, New York, pp 513-564 
Baleriaux D (1999) MRI of spinal cord diseases, 2nd edn. Lasion, 
(educational CD-ROM) Aartselaar, Belgium 
Brotchi J, Dewitte 0, Levivier M, Baleriaux D, Vandesteene A, 
Raftopoulos C, Flament Durand J, Noterman J (1991) A sur- 
vey of 65 tumors within the spinal cord: surgical results and 
the importance of preoperative magnetic resonance imaging. 
Neurosurgery 29:651-657 

Bourgouin PM, Lesage J, Fontaine S, Konan A, Roy D, Bard C, Del 
Carpio O’Donovan R (1998) A pattern approach to the differ- 
ential diagnosis of intramedullary spinal cord lesions on MR 
imaging. AJR Am J Roentgenol 170(6): 1645-1649 
Brotchi J (2002) Intrinsic spinal cord tumor resection. 
Neurosurgery 50(5): 1059-1063 

Bydder GM, Brown J, Niendorf HP, Young IR (1985) Enhancement 
of cervical intraspinal tumors in MR imaging with intravenous 
gadolinium-DTPA. J Comput Assist Tomogr 9:847-851 
Colombo N, Kucharczyk W, Brant-Zawadzki M, Norman D, Scotti 
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IDKD 2004 



Spinal Trauma and Spinal Cord Injnry 

A.E. Flanders 

Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA, USA 



Introduction 

Spinal trauma is one of the most common maladies en- 
countered in the emergency room setting. This is espe- 
cially true in major trauma centers. While the majority of 
these patients requires minimal supportive care for liga- 
mentous or muscular sprain, a significant proportion of 
these patients will endure vertebral fractures, spinal in- 
stability, neurologic deficits and associated visceral in- 
jury depending upon the severity of the initial trauma and 
mechanism of injury. In the most severe cases, the patient 
develops a concomitant spinal cord injury. 

Spinal cord injury (SCI) is the most devastating con- 
sequence of spinal injury. Approximately 11 000 new 
cases of SCI occur each year in the United States; there 
are about 250 000 living survivors of SCI [1]. SCI pri- 
marily affects young males during their most productive 
years. The most common etiology of SCI includes motor 
vehicular collisions and falls, however, the proportion of 
SCI resulting from violence continues to rise in the 
United States. The cumulative medical expenses to care 
for the most severely injured patients (with high cervical 
injuries) can exceed one million US dollars per patient. 
Unfortunately, despite the incorporation of better passen- 
ger safety devices in automobiles and the increased pub- 
lic awareness of SCI, the overall incidence of SCI has not 
decreased appreciably. The average age of the typical SCI 
patient has increased in the past decade.[l] 

Imaging of Spinal Trauma 

The clinical management and diagnostic assessment of 
spinal trauma and spinal cord injury have changed dras- 
tically in the past decade. Clinicians primarily rely on 
imaging modalities to diagnose and classily spinal-in- 
jured patients. While pluridirectional tomography and 
myelography have given way to more modem techniques 
such as computed tomography (CT) and magnetic reso- 
nance imaging (MRI), plain radiography is the primary 
method for assessing bony injury in spinal trauma. The 
recommended minimum radiographic evaluation of the 



injured spine includes good quality anteroposterior (AP) 
and lateral views. In the cervical region, special attention 
must be given to the Cl -2 articulation and to the cervi- 
cothoracic (C7-T1) junction. CT evaluation is mandatory 
for instances in which a portion of the spine is obscured 
on radiography or when the findings are equivocal. 

The advent of multidetector computed tomography 
(MDCT) has changed the clinical landscape for evalua- 
tion of spinal injury. The limitation or trade-off for sin- 
gle-detector CT study of the spine was in-plane resolu- 
tion for coverage; that is, in order to obtain high resolu- 
tion isotropic voxels of the spine (suitable for generation 
of reformatted images), only a limited area of coverage 
was possible. Alternatively, if a large section of the spine 
needed to be interrogated, it could only be accomplished 
at lower resolution. Multidetector CT permits both 
greater slice resolution and increased coverage. The 
isotropic voxels that are created from the volumetric 
dataset are suitable for reconstmctions at an infinite num- 
ber of projections. 

The much larger imaging datasets of MDCT have cre- 
ated an even greater need for digital manipulation, review 
and storage of the resulting imagesets. Formerly, a 3-mm 
single-slice CT study of the entire cervical spine would 
result in the creation of 35-45 images. A volumetric 
dataset created on an MDCT unit at sub-millimeter reso- 
lution can result in studies that exceed 150 images. 
Review of image sets of this size in multiple window set- 
tings can be imwieldy on film. For this reason, digital re- 
view on a PACS workstation is a more time-efficient 
method to review these large datasets. Moreover, since 
the datasets are volumetric and isotropic, reformatted im- 
ages can be produced that are of the same resolution as 
the original dataset. 

MRI 

Magnetic resonance imaging (MRI) has had a tremen- 
dous impact on the clinical evaluation of spinal and 
spinal cord injured patients. In the era of radiography, as- 
sessment of the bony axis was used to predict the in- 




190 



A.E. Flanders 



tegrity of the surrounding soft tissues (e.g. intervertebral 
disks, ligaments) as these structures are not visible on ra- 
diography. Besides evaluation of bony alignment, assess- 
ment of the stability of the injury (e.g. malalignment pro- 
duced by normal motion) is an integral part of the initial 
analysis of the injury [2]. Spinal instability is dependant 
upon the integrity of the ligamentous complexes. 
Stability of the injured segment may be suggested by in- 
ference based upon the degree of bony injury seen on ra- 
diography. A number of the fracture classification sys- 
tems based on radiography were used to give the proba- 
bility of ligamentous rupture. While CT improved our 
ability to identify and characterize subtle fractures and 
large soft tissue abnormalities (e.g. large paravertebral 
hematomas), most of the soft tissue abnormalities re- 
mained hidden. 

MRI has changed the way radiologists and clinicians 
view spinal injury because it depicts the entire spectrum 
of injury, notably the entire soft tissue component of in- 
jury. An understanding of the soft tissue characteristics of 
the injury is essential to diagnosis but it is imperative in 
surgical planning. Moreover, MRI is the only imaging 
modality that reveals the internal architecture of the 
spinal cord. Since the spinal cord is regularly evaluated 
when the spine is imaged, the clinical focus has changed 
from the spine to the spinal cord. 

The diagnostic MR spectrum of spinal injury can be 
divided into six separate distinct categories: bony injury, 
disk disruption or herniation, ligamentous injury, vascu- 
lar injury, epidural or paravertebral fluid collections, and 
spinal cord injury. 

Osseous Injury 

While there is no replacement for plain radiography or 
CT for the detection of fractures, MRI has certain unique 
advantages in the setting of spinal trauma. Multidetector 
CT with multiplanar reformations is the most complete 
and sensitive method for characterizing fractures. 
Cortical discontinuity can be difficult to identify on MRI 
without obvious loss of stature of the vertebral body or 
buckling of the cortical margin. However, a principal 
shortcoming of both radiography and CT is their inabil- 
ity to predict the age or chronicity of a fracture defor- 
mity. Acute fractures and significant compressive in- 
juries to bone without obvious fracture produce injury to 
the trabecular network of bone, resulting in microhem- 
orrhages. Because MRI is uniquely sensitive to subtle 
changes in water content, it can be used to locate subtle 
areas of fracture or compressive injury [3, 4]. The ab- 
normal marrow in the injured vertebral body is of lower 
signal intensity on T1 -weighted images, reverting to hy- 
perintensity on T2-weighted images. MRI has proven 
useful in distinguishing chronic and acute insufficiency 
fractures in addition to identifying “damaged” vertebral 
levels that have endured the compressive effects of in- 
jury [5]. 



Ligamentous Injury 

The ligamentous complexes that encase the vertebral col- 
umn provide stability to the spine and are the critical 
components that allow the rigid bony components the 
characteristic of mobility while maintaining stability. As 
the ligaments are not visible on radiography and poorly 
delineated on CT, they are not routinely assessable with 
these modalities. Therefore, fracture classification 
schemas were devised to predict the integrity of the liga- 
mentous complexes based on the pattern of bony injury 
to predict the probability of stability for a particular in- 
jury type [6, 7]. MRI is the only imaging modality which 
allows direct visual inspection of the ligaments and their 
relationship to the adjacent bony elements. The connec- 
tive tissues that comprise the ligaments are of low signal 
intensity on all pulse sequences. The anterior and poste- 
rior longitudinal ligaments form a long, low-signal con- 
tinuous band along the ventral and dorsal surfaces, re- 
spectively, of the vertebral bodies. The ligamentum 
flavum defines a continuous undulating low signal band 
along the ventral surface of the lamina. The posterior lig- 
amentous complex (intraspinous and supraspinous liga- 
ments) bridges the spinous processes. Ligament disrup- 
tion is characterized by a discontinuity in the contour of 
ligament that is best identified on the sagittal T2-weight- 
ed images. Fat suppression is useful to augment the sig- 
nal changes from damage to these connective tissues. The 
disrupted ligament may be identified in association with 
a prevertebral fluid collection in the setting of an anteri- 
or longitudinal ligament disruption or increased signal in 
the posterior paraspinal musculature in association with a 
posterior ligamentous complex disruption. Ligamentous 
disruption on MRI has a high correlation with surgical 
evaluation in thoracolumbar injuries [8]. 

Disk Injury and Herniation 

Post-traumatic disk abnormalities are classified as injuries 
and herniations. Simple disk injuries occur as a result of 
tearing of the annulus or nuclear fibers. The disk exhibits 
abnormal, increased signal intensity on T2-weighted im- 
ages relative to the adjacent disk spaces. Frequently, the 
disk space will be asymmetrically widened as a secondary 
sign of injury. Post-traumatic disk herniations have a sim- 
ilar appearance to disk herniations from a degenerative 
etiology; a polypoid extension of disk material in a sub- 
ligamentous location. The incidence of post-traumatic 
disk herniation is quite varied in the published literature 
[9, 10]. However, the incidence of disk herniations overall 
is greater since MRI has come into general use. 

Epidural Hemorrhage 

Post-traumatic extra-axial hemorrhages in the spine occur 
in up to 40% of all cases of spine trauma. The most fre- 




Spinal Trauma and Spinal Cord Injury 



191 



quent cause is tearing of the epidural venous plexus re- 
sulting in a epidural hematoma. The epidural space offers 
no relative resistance to the spread of the hemorrhage, so 
that the hematoma usually extends over many vertebral 
levels. Therefore, even when large in volume, spinal 
epidural hematomas frequently are clinically insignifi- 
cant as they do not compress the spinal cord. In certain 
circumstances, the hematoma may compress the thecal 
sac enough to warrant emergent surgical evacuation. 
Patients with intrinsic coagulopathy and ankylosing 
spondylitis have a higher incidence of dorsal epidural 
hematomas. 



Vertebral Artery Injury 

Vertebral artery dissection with thrombosis is a relatively 
common complication associated with cervical spinal in- 
jury. Rotational and translational forces applied to the 
fixed portions of the vertebral artery (contained within the 
foramen transversarium) damage the vascular intima dur- 
ing cervical injury. The reported incidence of vertebral 
artery injury is variable. Some arteriographic studies sug- 
gested that the vertebral artery is damaged in over 50% of 
all cervical spine fractures [11, 12]. Studies that use mag- 
netic resonance angiography (MRA) suggested that post- 
traumatic thrombosis of the vertebral artery occurs in al- 
most 25% of cases. In the majority of cases, the injury is 
clinically asymptomatic. Therefore, addressing this asso- 
ciated injury therapeutically remains controversial. 

Spinal Cord Injury 

MRI offers the only evaluation of spinal cord injury. MRI 
has been shown to be highly sensitive to a broad range of 
injury patterns in both humans and animal models of 
SCI. There are three fundamental MRI findings of SCI: 
spinal cord swelling, edema and hemorrhage. 
Collectively, the presence and extent of these injury pat- 
terns highly correlate to the neurologic deficit and prog- 
nosis for clinical recovery. 

Spinal cord swelling is the non-specific enlargement 
of the caliber of the spinal cord at the level of injury. 
Since this finding refers to an alteration in shape of the 
spinal cord, it is visible on all pulse sequences. The length 
of spinal cord that exhibits swelling is directly propor- 
tional to the degree of neurologic deficit. 

Spinal cord edema on MRI correlates to an increase in 
intramedullary fluid (intracellular or extracellular) in the 
injured tissues. This appears as a spindle-shaped area of 
increased signal intensity on T2-weighted images. The 
edema spans a variable length of the spinal cord in pro- 
portion to the severity of the neurologic deficit. Edema is 
invariably present in all cases where post-traumatic 
myelopathy is present. The entire cervical spinal cord 
may be edematous in the most severe neurologic deficits. 
The length of the initial injury is inversely proportional 



to the degree of neurologic recovery at 12 months in the 
upper and lower extremities [13-16]. 

Post-traumatic spinal cord hemorrhage on MRI corre- 
lates histologically with coalescent areas of hemorrhagic 
necrosis after injury. Although hemorrhage is always 
identified on histologic preparations of spinal cord injury, 
it is only identified on clinical MRI when a focal clot is 
produced. The hemorrhage has a propensity to collect in 
the central gray matter of the spinal cord. On MRI, herh- 
orrhagic features of SCI appear as foci of low signal in- 
tensity on T2-weighted and gradient-echo pulse se- 
quences. The hemorrhage is generally found at the geo- 
graphic epicenter of the spinal cord injury with the ede- 
ma spaiming a variable distance above and below the epi- 
center. The anatomic location of the hemorrhage corre- 
lates to the neurologic level of injury better than either 
edema or swelling. Hemorrhage correlates with the most 
severe neurologic injuries. Moreover, the presence of a 
focal hemorrhage at the injury epicenter portends for a 
poor neurologic recovery at one year [13-16]. 

Chronic Spinal Cord Injury Evaluation 

Neurologic recovery following SCI is variable and is de- 
pendant on a multitude of factors including: the severity 
of the initial neurologic deficit, mechanism of injury, in- 
juries associated with the central nervous system (CNS), 
level of multidisciplinary expertise in caring for SCI pa- 
tients, early restoration and fixation of spinal alignment 
(controversial), administration of steroids (controversial) 
and aggressive rehabilitation. In the majority of cases, the 
full extent of potential neurologic recovery will be real- 
ized within a year after injury. The phenomenon of acute 
neurologic deterioration following a stable period of a 
persistent neurologic deficit is known as post-traumatic 
progressive myelopathy (PTPM). The imaging manifesta- 
tions of this clinical syndrome are varied and include: 
progressive spinal cord atrophy, myelomalacia, sy- 
ringomyelia and tethering. The latter two entities are the 
conditions amenable to surgical intervention. Surgery can 
halt the progression of the myelopathy and, in some in- 
stances, restore the patient to their former neurologic 
state [17, 18]. 

Future Applications 

MRI will continue to play a major role in the acute and 
chronic evaluation of spinal and spinal cord injury. MRI 
plays an integral role in the clinical evaluation and surgi- 
cal decision process at all SCI centers. The application of 
functional MRI techniques to diseases of the spinal cord 
is just being realized. This is technically challenging due 
to the small inherent size of the target (less than 1 cm in 
diameter) and the associated problems from cerebrospinal 
fluid (CSF) pulsation and proximity to bone, which tend 
to degrade image quality. As the physiologic techniques of 




192 



A.E. Flanders 



diffusion, spectroscopy and BOLD (fMRI) for the spine 
become more clinically accessible, physicians will be able 
to gauge the degree of salvageable tissue with greater pre- 
cision. MRI has already shown promise is assessing via- 
bility of spinal cord transplants. Diffusion tensor imaging 
(DTI) techniques and tractography may ultimately prove 
to be the most robust methods for gauging the proportion 
of survivable neurons and for assessing response to new 
therapies (e.g. transplants) [19-21]. 

References 

1. - (2000) Spinal cord injury: facts and figures at a glance. J 
Spinal Cord Med 23:51-53 

2. White AA III, Panjabi MM (1978) Clinical biomechanics of 
the spine. JB Lippincott, Philadelphia 

3. Levitt MA, Flanders AE (1991) Diagnostic capabilities of 
magnetic resonance imaging and computed tomography in 
acute cervical spinal column injury. Am J Emerg Med 
9(2):131-135 

4. Tarr RW, Drolshagen LF, Kerner TC, Allen JH, Partain CL, 
James AE (1987) MRI imaging of recent spinal trauma. J 
Comput Assist Tomogr 1 1(3):412-417 

5. Baker LL, Goodman SB, Perkash I, Lane B, Enzmann DR 
(1990) Benign versus pathologic compression fractures of 
vertebral bodies: assessment with conventional spin-echo, 
chemical shift, and STIR MRI imaging. Radiology 174:495- 
502 

6. Holdsworth F (1970) Fractures, dislocations and fracture-dis- 
locations of the spine. J Bone Joint Surg Am 52:1534-1551 

7. Denis F (1983) The three column spine and its significance in 
the classification of acute thoracolumbar spinal injuries. Spine 
8:817-831 

8. Lee HM, Kim HS, Kim DJ, Suk KS, Park Jo, Kim NH (2000) 
Reliability of magnetic resonance imaging in detecting poste- 
rior ligament complex injury in thoracolumbar spinal frac- 
tures. Spine 25(16):2079-2084 

9. Rizzolo SJ, Piazza MRI, Cotier JM, Balderston RA, Schaefer 



DM, Flanders AE (1991) Intervertebral disc injury complicat- 
ing cervical spine trauma. Spine 16(6): 187- 189 

10. Harrington JF, Likavec MJ, Smith AS (1991) Disc herniation 
in cervical fracture subluxation. Neurosurgery 29:374-379 

11. Friedman DP, Flanders AE (1992) Unusual dissection of the 
proximal vertebral artery: description of three cases. AJNR 
Am J Neuroradiol 13:283-286 

12. Friedman DP, Flanders AE, Thomas C, Millar W (1995) 
Vertebral artery injury after acute cer\ical spine trauma: rate 
of occurrence as detected by MR angiography and assessment 
of clinical consequences. AJR Am J Roentgenol 164:443-447 

13. Marciello M, Flanders AE, Herbison GJ, Schaefer DM, 
Friedman DP, Lane JI (1993) Magnetic resonance imaging re- 
lated to neurologic outcome in cervical spinal cord injury. 
Arch Phys Med Rehabil 74:940-946 

14. Flanders AE, Spettell CM, Tartaglino LM, Friedman DP, 
Herbison GJ (1996) Forecasting motor recovery after cervical 
spinal cord injury: value of MR imaging. Radiology 201:649-55 

15. Schaefer DM, Flanders AE, Osterholm JL, Northrup BE (1992) 
Prognostic significance of magnetic resonance imaging in the 
acute phase of cervical spine injury. J Neurosurg 76(2):2 18-223 

16. Flanders AE, Spettell CM, Friedman DP, Marino RJ, Herbison 
GJ (1999) The relationship between the functional abilities of 
patients with cervical spinal cord injury and the severity of 
damage revealed by MR imaging. AJNR Am J Neuroradiol 
20:926-934 

17. Barnett HJM, Botterell EH, Jousse AT, Wynn-Jones M (1966) 
Progressive myelopathy as a sequel to traumatic paraplegia. 
Brain 89:159-173 

18. Rossier AB, Foo D, Shillito J et al (1981) Progressive late post- 
traumatic syringomyelia. Paraplegia 19:96-97 

19. Ford JC, Hackney DB, Alsop DC et al (1994) MRI character- 
ization of diffusion coefficients in a rat spinal cord injury 
model. Magn Reson Med 31:488-494 

20. Schwartz ED, Yezierski RP, Pattany PM, Quencer RM, Weaver 
RG (1999) Diffusion- weighted MR imaging in a rat model of 
syringomyelia after excitotoxic spinal cord injury. AJNR Am J 
Neuroradiol 20(8): 1422-1428 

21. Madi S, Vinitski S, Flanders AE, Nissanov J (2001) Functional 
imaging of the human spinal cord. AJNR Am J Neuroradiol 
22(9): 1768-1774 




IDKD 2004 



Spinal Inflammation and Demyelinating Diseases 

C. Manelfe 

Department of Diagnostic and Therapeutic Neuroradiology, Hopital Purpan, Toulouse, France 



Introduction 

Clinical presentation and imaging findings of spinal in- 
flammatory and demyelinating diseases are protean and 
often non-specific. They may mimic neoplastic lesions 
either clinically or radiologically. Magnetic resonance 
imaging (MRI) is the best imaging modality to screen pa- 
tients who are clinically suspected of having myelitis. 

The most challenging imaging presentation is that of 
an enlarged spinal cord. Enlargement or gadolinium en- 
hancement of the spine are not synonymous with spinal 
cord tumor and can be observed in patients with myelitis, 
myelopathy or syringohydromyelia. 

The words myelitis and myelopathy are often used in- 
terchangeably, are not specific and describe various 
pathologic conditions of the spinal cord. Myelopathy usu- 
ally indicates a noninflammatory, degenerative disorder 
of the spinal cord resulting from compressive, vascular, 
toxic or metabolic insults. Myelitis results from inflam- 
matory or infectious disorders (mainly viral), or pre- 
sumed autoimmune or idiopathic conditions [1,2]. 

The clinical presentation of the patient, anamnesis, 
mode of onset, and duration can orient the diagnosis: 

- An acute or rapidly progressive clinical onset may have 
a vascular, infectious, viral or inflammatory origin; 

- A slowly progressive onset is more likely due to com- 
pression, demyelination, vascular, metabolic or toxic 
etiologies. 

Serologic and culture examinations of blood and cere- 
brospinal fluid (CSF), and biopsy specimens (skin, lymph 
nodes, etc.) may obviate surgical biopsy of the spinal cord. 

Imaging Techniques 

Among the various imaging modalities, MRI is the best 
technique due to its multiplanar capabilities and superior 
tissue sensitivity. MRI allows clinicians to answer the fol- 
lowing questions: (1) Is the spinal cord normal or not? (2) 
Is the lesion localized to the cord (focal or diffuse) or to 
the whole neuraxis (brain, nerve roots, etc.)? (3) How is 
the signal? Is there an enhancement or not? 



Some of the most common sequences are herein de- 
scribed: 

- Sagittal and axial Tl- and T2-weighted fast spin echo 
(FSE) sequences are the most frequently used. Spin 
echo (SE) sequences are superior to gradient echo 
(GE) sequences except when associated acute hemor- 
rhage is suspected. The study of patients with suspect- 
ed intramedullary lesions (mainly from multiple scle- 
rosis) is improved by including separate sagittal proton 
density- weighted FSE scans which generally confirm 
the lesions suspected on the T2-weighted sequences 
and frequently may detect additional cord lesions [3]. 

- FSE sequences with longer repetition time (TR=3000 
ms) and echo time (TE=150 ms) have poorer lesion- 
cord contrast than those with more moderate parameters 
(TR=2500 ms, TE=90 ms) [4]. Slice thickness must be 
3 mm or less when a spinal cord lesion is suspected. 

- SE sequences with short time inversion recovery 
(STIR) technique (TR=3000 ms; TE=40 ms; inversion 
time, TI=140-I60 ms) are well suited for detecting in- 
tramedullary lesions and are particularly helpful in de- 
tecting multiple sclerosis plaque [3, 4]. 

- Sequences with long TI (e.g. FLAIR with TR=10 000 
ms, TE=180 ms and TI=2000 ms) are less sensitive in 
detecting intramedullary lesions but can be useful to 
differentiate intramedullary cyst from myelomalacia or 
edema. 

- In the axial plane, T2-weighted SE sequences are more 
sensitive to flow artifacts, while T2* -weighted GE se- 
quences are more efficient, mainly at the cervical level. 

- Gadolinium injection increases lesion conspicuity and 
imaging specificity, and improves localization and de- 
tection of subtle areas of infection or inflammation. 
Post-gadolinium fat-suppressed Tl -weighted sequences 
are useful for imaging not only bone marrow and 
epidural space, but also spinal cord and nerve roots. 

- Magnetic resonance angiography (MRA), also called 
black blood technique, of the spinal cord needs in- 
creased spatial resolution and presently, cannot replace 
spinal cord angiography when medullary vessels are 
not dilated. Gadolinium-enhanced MRA has increased 
spatial resolution and is giving promising results [4]. 




194 



C. Manelfe 



- Magnetic resonance myelography (MRM) using ul- 
trafast techniques such as HASTE (half Fourier ac- 
quisition single shot turbo spin echo) sequence or 
CISS (constructive interference steady state) 3D se- 
quence is a valuable method to explore spine and 
spinal cord pathology. It is, however, less useful in 
imaging intramedullary pathology than intra-ex- 
tradural lesions (e.g. tumors, degenerative disk dis- 
ease, spinal stenosis). 

- Diffusion-weighted imaging (DWI) is still in evalua- 
tion. Anisotropic diffusion shows the microscopic ar- 
chitecture of the parenchyma and depicts losses of 
anisotropy probably due to axonal loss at an early 
stage. In the future, DWI may be used to detect or eval- 
uate spinal cord ischemia, spondylotic myelopathy and 
cord trauma [5]. 

Intramedullary lesions represent the most difficult sit- 
uation for the clinician and the radiologist. Myelitis may 
mimic spinal cord tumor and vice versa [2, 6]. As caus- 
es of myelitis, demyelinating and viral diseases are the 
most frequent. MRI is sensitive but lacks specificity: 
most lesions feature high signal intensity on T2-weight- 
ed images. Gadolinium injection improves specificity 
but a lack of enhancement does not definitely rule out 
tumor. 



Demyelinating Diseases 

Multiple Sclerosis 

Multiple sclerosis (MS) is the most frequent demyelinat- 
ing disease of the central nervous system of autoimmune 
origin. MS affects young adults and has 3 main clinical 
forms: (a) relapsing-remitting, (b) secondary progressive, 
and (c) primary progressive. Diagnosis is based on clini- 
cal history, physical examination and paraclinical tests, 
such as CSF analysis, cortical evoked responses and MRI 
findings. MRI is advantageous in that it demonstrates le- 
sions in vivo; previously these lesions could only be show 
at autopsy [7-9]. 

Approximately 10%-15% of patients with spinal cord 
plaques have no intracranial disease. MS affects mainly 
the cervicothoracic cord: plaques are elongated, extend 
over 1-2 vertebral segments, and do not respect bound- 
aries between tracts of gray and white matter. Cord en- 
largement may be noted in acute lesions and gadolinium 
enhancement may be observed. 'On axial sections, 
plaques are located at the periphery of the cord mainly in 
the posterior (41%) and lateral (25%) aspects. More than 
half of cord plaques longer than two vertebral segments 
are accompanied by cord atrophy or, alternatively, by 
cord swelling [4, 7]. 

Diffuse cord abnormalities seem to correlate with pri- 
mary or secondary progressive clinical MS subtypes. 
Diffuse disease is more frequently associated with cord 
atrophy and has a weak but significant correlation with 
clinical disability [10]. 



The magnetization transfer ratio (MTR) in cervical 
cord of MS patients may be reduced compared to that in 
normal controls, even in the absence of detectable cord 
lesions on T2-weighted sequences [11]. 

Differential diagnosis with neoplasm, granulomatous 
infections and viral diseases may be difficult. The disap- 
pearance of enhancing lesions on follow-up examinations 
and associated brain lesions suggest the diagnosis of MS. 

Acute Disseminated Encephalomyelitis 

Acute disseminated encephalomyelitis (ADEM) is an acute 
or subacute demyelinating process of autoimmune origin 
mediated by antibody-antigen complexes. It has a 
monophasic course, typically following a specific viral ill- 
ness, vaccination or non-specific respiratory infection. The 
mortality rate is approximately 10%-20% in the acute 
phase, but 60% of patients recover completely [12]. 
Pathological analysis shows perivenous demyelination with 
variable inflammatory cell infiltration of the white matter. 

MRI of patients with ADEM gives non-specific re- 
sults, showing extended and multifocal high signal inten- 
sity on T2 -weighted images in the white matter. In the 
brain, lesions are usually bilateral, asymmetric, widely 
distributed without mass effect. Involvement of the basal 
ganglia and thalami has been reported [13]. A monopha- 
sic course of disease and gadolinium enhancement of all 
lesions help to differentiate ADEM from MS [12]. 

Granulomatous Diseases 

Sarcoidosis is an idiopathic, multisystemic, noninfectious 
granulomatous disease. Spinal cord involvement is pre- 
sent in 6%-8% of cases of neurosarcoidosis. The clinical 
picture is non-specific and clinical and laboratory tests 
are mandatory (e.g. Kvein skin test, serum levels of an- 
giotensin-converting enzyme (ACE), CSF studies, chest 
radiography). Histologic examination of biopsies of skin, 
nasal mucosa and lymph nodes is of great value and can 
obviate the need for cord biopsy. As in MS, cervical cord 
involvement is frequent in spinal sarcoidosis. Tl- andT2- 
weighted images are not specific, and show an enlarged 
cord and hyperintensity on T2-weighted images, mimic- 
king a tumor or an MS plaque [2, 6]. Four patterns of en- 
hancement [14] correspond to different stages of the dis- 
ease: (a) linear, leptomeningeal; (b) parenchymal, associ- 
ated with cord swelling; (c) focal or multifocal with ab- 
normal cord; and (d) atrophy. Associated leptomeningeal 
cranial involvement is helpful for the diagnosis of sar- 
coidosis but may also be present in tuberculosis or non- 
Hodgkin’s lymphoma. 

Involvement of the spinal cord in Lyme disease, due to 
Borrelia burgdorferi infection, is rare. Lymphocytic 
meningoradiculitis and acute transverse myelopathy (dis- 
cussed later) are the most common clinical presentations. 
Leptomeningeal enhancement of the spinal cord, nerve 
roots and cranial nerves is usual [15]. 




Spinal Inflammation and Demyelinating Diseases 



195 



Other infectious granulomatous diseases, such as tu- 
berculosis and syphilis, give MRI findings similar to 
those of sarcoidosis. 



Nongranulomatous Diseases 

The class of nongranulomatous diseases comprises vi- 
ral, bacterial and parasitic infections as well as toxic 
myelopathies. 

Acute Transverse Myelitis 

The clinical picture is frequently represented by an acute 
transverse myelitis (ATM) which can result from autoim- 
mime or allergic response, vasculitis, direct viral invasion or 
demyelination [9]. Transverse myelitis is an inflammatory 
or infectious process involving the entire cross-sectional 
area of the cord at a particular level. The most prominent 
findings on histopathological examination are found in the 
blood vessels and the perivascular spaces of the gray and 
white matter: hyperemia, perivascular cellular exudate and 
edema, and hemorrhage [16]. Acute paraparesis, with mo- 
tor, sensory and sphincter disorders, is the most common 
clinical presentation. In children, ATM is commonly pre- 
ceded by infection (e.g. herpes, rabies, varicella, mumps, 
rubeola) or vaccination. In adults, the most frequent causes 
of ATM are acquired immune deficiency syndrome 
(AIDS), vasculitis (lupus) and paraneoplastic syndromes. 

The MRI appearance of transverse myelitis is non-spe- 
cific. Focal or extended cord enlargement is present in 
40% of case and gadolinium enhancement is seen in 
60%. On axial sections, the high signal intensity on T2- 
weighted images occupies more than two-thirds of the 
cross section of the cord [17]. 

AIDS Myelopathies 

Patients infected with human immunodeficiency virus 
(HIV) frequently experience vacuolar myelopathy, HIV 
myelitis, opportunistic infections, lymphomas, and vas- 
cular and metabolic disorders [18]. 

Vacuolar myelopathy is the most common spinal cord 
disease in patients with AIDS (30%-50% in autopsy stud- 
ies [19, 20]). It is characterized by a spongy degeneration 
of spinal white matter, affecting predominantly the later- 
al and posterior columns of the thoracic cord. 
Histopathological features are similar to those of suba- 
cute combined degeneration of the spinal cord secondary 
to vitamin B12 deficiency [19, 21]. Common clinical 
manifestations are progressive spastic paraparesis, incon- 
tinence and ataxia. Dementia is observed in 70% of cas- 
es [19, 20]. MRI usually shows diffuse and symmetric 
hyperintensities on T2-weighted images on the dorsal 
columns in a normal or atrophic spinal cord, more often 
without gadolinium enhancement. 

HIV myelitis occurs in 5%-8% of AIDS patients and is 
caused by direct HIV infection. Lesions are focal, have 



high signal intensity on T2-weighted images, and pre- 
dominate in the central gray matter. 

Opportunistic infections in AIDS patients may be 
caused by cytomegalovirus (CMV), fungi, herpes sim- 
plex virus and varicella-zoster virus (VZV); other com- 
mon opportimistic infections are tuberculosis, toxoplas- 
mosis, syphilis and progressive multifocal leucoen- 
cephalopathy [20-22]. CMV infection, the most common 
opportunistic infection, frequently involves the conus and 
cauda equina [4, 20, 22]. Back and radicular pain, flaccid 
paraparesis, urinary retention, saddle anesthesia and in- 
flammatory CSF profile (polymorphonuclear pleocyto- 
sis, low sugar and high protein contents), are usual [4, 
16]. VZV myelitis may follow cutaneous vesicular erup- 
tion. Infection involves the posterior horns and dorsal 
root ganglia. 

In AIDS patients, when focal spinal cord enlargement 
with gadolinium enhancement is present, toxoplasmic 
myelitis and lymphoma should be considered; brain in- 
volvement is present in both conditions, but a positive 
thallium-201 SPECT scan makes a diagnosis of lym- 
phoma more likely [20]. When spinal cord enlargement 
and abnormal signal (hyperintensity on T2-weighted im- 
ages) are associated with meningeal enhancement, CMV 
infection and tuberculosis should be considered [17]. 

Tropical Spastic Paraparesis 

Infection with human T-cell lymphotrophic virus type I 
(HTLV-I), endemic in the Carribean and in some parts of 
Africa, is called tropical spastic paraparesis (TSP) [23]. 
In Japan, this myelopathy was found to be associated with 
leukemia and was thus called HTLV-l-associated 
myelopathy [23]. Neuropathology reveals demyelination 
in the lateral and dorsal tracts as well as axonal loss. 
Clinical presentation usually consists of progressive 
weakness of the lower limbs with paresthesias. 

MRI may show either diffuse atrophy and abnormal 
signal intensity on T2-weighted images or, at the acute 
stage, spinal cord swelling with peripheral gadolinium 
enhancement [24]. Associated white matter lesions in the 
brain have been reported [16]. 

Bacterial and Parasitic Infections 

Bacterial infections and abscesses of the spinal cord are 
extremely rare [25]. Clinical presentation can be acute, 
subacute or chronic; the infection may mimic tumor. 
Predisposing factors include cardiopulmonary infections, 
immunosuppression and drug abuse [26]. The most com- 
mon causative agent is Staphylococcus aureus. Cord 
swelling and extensive edema are present at the initial 
stage (phlegmon). A rim-enhancing cavity is seen atat the 
abscess stage. Listeria monocytogenes can cause ab- 
scesses in the brain stem and upper cervical cord. 

Parasitic infections such as schistosomal myelitis, tox- 
ocariasis, bilharziosis, and cysticercosis are suspected in 
patients who have been in countries where these diseases 




196 



C. Manelfe 



are endemic, and in patients who have hypereosinophilia 
(in blood or CSF). Spinal cord lesions are far less fre- 
quent than brain lesions. 

MRI shows non-specific focal mass effect, low signal 
intensity on T1 -weighted images and high signal intensi- 
ty on T2-weighted images. Cysts in the subarachnoid 
spaces compressing the spinal cord or nerve roots are 
seen in neurocysticercosis; their mobility in the CSF can 
be helpful for the diagnosis of cysticercosis. 

Metabolic and Nutritional Deficiency Myelitis 

Subacute combined degeneration of the cord is due to vita- 
min B12 deficiency and is often associated with mega- 
loblastic anemia [16]. Degenerative and demyelinating 
changes occur in the white matter of the dorsal and lateral 
columns of the spinal cord. MRI shows hyperintensity on 
T2-weighted images in the dorsal columns (mainly cervical 
and thoracic) with or without cord enlargement or gadolin- 
ium enhancement [27]. Following vitamin B12 supplemen- 
tation, improvement is seen clinically and on MRI. 

Radiation Myelitis 

Atrophy is the most common appearance of radiation 
myelitis. It can mimic, however, tumoral infiltration when 
transient enlargement of the cord with high signal inten- 
sity on T2-weighted images is present. Focal enhance- 
ment after gadolinium administration may be seen. The 
thoracic cord is more sensitive to radiation. A spinal le- 
sion attributed to radiation myelitis should lie in the radi- 
ation portal and appear at least 6 or 12 months after ra- 
diotherapy. Associated bony changes (e.g. fatty degener- 
ation of the vertebral bodies) in the radiation portal help 
in differentiating myelitis from tumor. Overall, 82% of 
cases of radiation myelitis are related to tumors of the 
head and neck [6]. 



References 

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AB, Baker LH (eds) Clinical neurology. Harper Row, 
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2. Manelfe C (1992) Imaging of the spine and spinal cord. Raven, 
New York 

3. Dietemann JL, Thibaut-Menard A, Warter JM et al (2000) 
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4. Finelli DA, Ross JS (2000) MR imaging of intrinsic inflam- 
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5. Pattany PM, Puckett WR, Klose KJ et al (1997) High resolu- 
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9. Tartaglino LM, Croul SE, Flanders AE, Sweeney ID, 
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16. Byrne TN, Benzel EC, Wasman SG (2000) Diseases of the 
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20:1412-1416 

18. Barakos JA, Mark AS, Dillon WP, Norman D (1990) MR 
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IDKD 2004 



Spinal Inflammation and Demyelinating Diseases 

M. Leonardi, M. Maffei 

Neuroradiology Service, Bellaria Hospital, Bologna, Italy 



Introduction 

Diagnosis of spinal inflammatory disease is a eomplex 
proeess requiring an appraisal of elinieal, laboratory and 
neuroradiological findings. Spinal inflammation ean be di- 
vided into tw^o groups: diseases affecting the vertebral bod- 
ies and intervertebral disks, and diseases of the spinal cord. 

Vertebral and Disk Space Infection 

Tuberculosis 

Tuberculosis (Figs. 1-5) is the most common cause of 
vertebral body infection; 75% of cases of tuberculous 



spondylitis occur prior to age 20 years. In most instances, 
vertebral body involvement is secondary to hematoge- 
nous spread of Mycobacterium tuberculosis from a pul- 
monary source, which more often than not remains qui- 
escent. Disease onset is insidious and its course is more 
benign than that of pyogenic osteomyelitis. Clinical pre- 
sentation is usually non-specific. Patients describe long- 
term back pain. Vague abdominal pain related to involve- 
ment of sympathetic nerves by a paravertebral mass may 
be the only symptom. Spinal cord and root compression 
with associated neurologic deficit due to epidural spread 
of the disease occurs in 10%-20% of patients. Paraplegia 
developing into Potf s disease is usually less severe and 
carries a better prognosis than that of pyogenic infections. 
The lower half of the spine is commonly involved. 




Fig. 1. Tuberculosis. Sagittal MR, Tl- 
weighted image: signal intensity alteration 
of two vertebral bodies and of the disc space 



Fig. 2. Tuberculosis. Sagittal MR, T2- 
weighted image: hyperintensity of vertebral 
bodies and of the disc space 



Fig. 3. Tuberculosis. Sagittal MR, Tl- 
weighted postgadolinium image: marked 
enhancement of the granulomatous tissue 




198 



M. Leonard!, M. Malfei 





Fig. 4a-d. Tuberculosis. Axial MR, T1 -weighted postgadolinium images: the granulomatous 
tissue involves the paravertebral structures and medially the epidural space 





Fig. 5. Coronal MR, T1 -weighted image of tuberculosis 



The infection first appears in the anterior parts of 
the vertebral body adjacent to a disk space. In about 
50% of cases, the infection spreads through the disk 
space to an adjacent vertebral body. Nonadjacent ver- 
tebral bodies can become involved secondarily to 
paraspinous or subligamentous spread of infection. In 
tuberculous spondylitis, involvement of posterior ele- 
ments is much less common than in pyogenic or fun- 
gal infection. New bone formation is more character- 
istic of pyogenic infection than tuberculosis. The mas- 
sive bone destruction in tuberculous spondylitis fre- 
quently results in gibbus deformity. Large often par- 
tially calcified paraspinal masses are a common fea- 
ture of tuberculous spondylitis, reflecting the protract- 
ed course of the disease. Bilateral psoas abscesses typ- 
ically accompany tuberculous spondylitis. Hallmarks 
identified on computed tomography (CT) or magnetic 
resonance imaging (MRI) include fragmentation and 
destruction of the anterior aspect of one or two adja- 
cent vertebral bodies, disk space narrowing, and 
paraspinal abscesses containing small calcifications. 
T1 and T2 relaxation times of the disk space and ver- 
tebral bodies involved are prolonged. 





Spinal Inflammation and Demyelinating Diseases 



199 



In the early stages that present only signal intensity al- 
teration and disk space narrowing, it may be difficult to 
distinguish between pyogenic and tuberculous os- 
teomyelitis. Culture of aspirated or biopsied material is 
essential, particularly when the appearance is not typical. 
Once a gibbus has developed, MRI is far superior to CT 
in disclosing the presence and degree of spinal cord com- 
pression. 

Intradural and intramedullary tuberculomas are rare. 
Clinical symptoms and imaging characteristics are indis- 
tinguishable from spinal neoplasms. 



Pyogenic Infections 

Pyogenic involvement of the vertebral body accounts for 
only 2%-4% of all cases of pyogenic osteornyelitis and 
usually arises in the lumbar region. Infection primarily 
involves the disk space in children and the vertebral body 
in adults. A disk space infection will rarely extend to the 
epidural and paravertebral spaces. 

Staphylococcus aureus accounts for approximately 
60% of adult infections, while Enterobacteriaceae, com- 
mon agents of urinary tract infection, account for about 
30%. The most frequent strain is Escherichia coli, fol- 
lowed by Pseudomonas aeruginosa and Klebsiella 
species. 

The earliest findings detectable on CT examination 
are irregularity and erosion of contiguous end plates as- 
sociated with narrowing of the disk space and dimin- 
ished attenuation of the vertebral body. The posterior 
elements are seldom involved. Later in the process, 
usually beginning at 10-12 weeks, an osteoblastic re- 
sponse may develop with sclerotic new bone formation. 
Progression of the osteoblastic response may result in 
eburnation of the vertebral bodies and subsequent fu- 
sion. If treatment is improper or incomplete, collapse 
of the vertebral affected bodies may ensue with result- 
ing gibbus deformity and instability of the vertebral 
column. 

Paravertebral soft tissue extension is observed in 
about 20% of patients with pyogenic osteomyelitis and 
diskitis. 

MRI is the most sensitive technique for detection of 
osteomyelitis and diskitis, and is the procedure of 
choice in evaluation of patients with suspected spine 
infection. Sagittal images are the most useful for 
demonstrating disk space and adjacent vertebral body 
involvement, whereas axial views demonstrate par- 
avertebral soft tissue extension. The disk space and 
portions of the vertebral bodies adjacent to the disk ex- 
hibit low signal intensity on images with long repeti- 
tion time (TR) and echo time (TE). With progressive 
involvement of the vertebral bodies, there is loss of the 
normal, well-delineated low signal of the vertebral end 
plates, and progressive loss of disk space height. 
Morphologic distinction between the disk and verte- 



bral body becomes increasingly difficult. Gd-DTPA 
administration is important for evaluating diskitis or 
osteomyelitis. Infection evokes intense uptake of con- 
trast material by both the disk and adjacent vertebral 
bodies and soft tissue. Any epidural or soft tissue 
spread is delineated in greater detail than in noncon- 
trast studies. 



Intramedullary Inflammatory Lesions 

Multiple Sclerosis 

Multiple sclerosis (MS) is a common demyelinating dis- 
ease of the central nervous system affecting white matter 
of the brain and spinal cord. MRI is the best imaging 
modality for direct visualization of intramedullary de- 
myelinating plaques in MS. Spinal MS lesions can pre- 
sent one of three appearances: segmental fusiform en- 
largement of the cord, most often in the cervical spine, an 
area of hyperintense signal on T2-weighted images with- 
out any changes in cord width, and cord atrophy. These 
three different appearances may represent the same lesion 
at three different stages. The segmental, usually subtle, 
enlargement of the spinal cord and high signal intensity 
seen on T2-weighted images in the acute phase can be 
linked to perivenous inflammation, interstitial edema, or 
microglial proliferation. 

The appearance of cord atrophy may correspond to the 
endstage of the disease. The yield of positive spinal MR 
scans is higher in acute (82%) than in chronic (61%) 
spinal cord syndromes; it is also higher in the cervical re- 
gion (86%) than in the thoracic (6%) and lumbar spine. 
Gd-DTPA administration has been used to differentiate 
active from inactive plaques. Delayed contrast enhance- 
ment of the lesions was seen in patients with clinically 
active disease, but no uptake could be detected in patients 
with stable disease. 

Transverse Myelitis 

Transverse myelitis, a condition generally encountered in 
younger age groups, characteristically develops as a 
rapidly progressing myelopathy. Generally, the myelitis 
regresses in 1-2 months, although in some patients a neu- 
rological deficit may persist. In many cases, transverse 
myelitis is related to a viral infection (herpes virus) and 
may also arise in patients with acquired immune defi- 
ciency syndrome (AIDS). MRI emphasizes diffuse cord 
enlargement but conflicting signal features are depicted 
on T2-weighted sequences. In all cases, areas of signal 
change show variable contrast uptake depending on acute 
stage and type of treatment. Lesion distribution results 
from the neurotropism of the causative virus and may 
help to identify the agent responsible. In any case, diag- 
nosis of myelitis is confirmed by isolation of the viral 
strain from the CSF (Figs. 6-8). 




200 



M. Leonard!, M. Maffei 




Fig. 6. Transverse myelitis. Sagittal MR, 
PD- weighted image: hyperintensity in mid- 
cervical cord; the cervical cord is moder- 
ately enlarged 



Fig. 7. Transverse myelitis. Sagittal MR, 
T2-weighted image: confirmation of the 
hyperintensity in midcervical cord 



Fig. 8. Transverse myelitis. Sagittal MR, 
T1 -weighted postgadolinium image: marked 
enhancement of the lesion 



Sarcoidosis 

This multisystem, noncaseating granulomatous disease of 
unknown origin involves the central nervous system in 
approximately 5% of cases. Spinal cord involvement is 
much rarer. Intramedullary involvement is seen in 35%, 
extramedullary involvement in 35%, involvement of both 
in 23%, and extradural involvement in 2%. 

Intramedullary swelling of the cervical and upper tho- 
racic cord is the most common finding on imaging stud- 
ies. This condition usually mimics intramedullary neo- 
plasm and is often confused with gliomas at surgery. 
Spinal sarcoidosis usually involves the leptomeninges. 

Neuro-Lupus and Neuro-Behget’s Disease 

Although neurological complications arise in 20%-50% 
of patients with systemic lupus erythematosus (SLE), 
myelitis is rare and only arises many years after diagno- 
sis of the disease. Neuropathologcal examination disclos- 
es areas of vacuolar degeneration in the spinal cord white 
matter, usually in the middle or lower thoracic spine, 
without clear signs of vasculitis. MRI features of spinal 
cord involvement in SLE are aspecific with single or 
multiple signal alterations on T2-weighted turbo spin 
echo (TSE) sequences. 

Behget’s syndrome is a multisystem disease of un- 
known cause. Neuropathological changes of the central 
nervous system (CNS) include areas of demyelination and 
glial proliferation associated with perivascular lympho- 



cyte infiltrate and wallerian degeneration. As there are no 
specific laboratory or instrumental tests for Behget’s dis- 
ease, diagnosis is based on major and minor clinical cri- 
teria, namely recurrent aphthous-type oral and genital ul- 
ceration and iritis with various skin lesions. CNS involve- 
ment is rare at onset, but may occur in 10%-50% of pa- 
tients. Neuro-Behget is characterized by a relapsing and 
remitting course similar to that of MS. Spinal cord in- 
volvement is clinically present in 10%-20% of cases. MRI 
findings are similar to those of MS and SLE myelitis and 
differential diagnosis cannot be based on imaging alone. 

Guillain-Barre Syndrome 

This acute inflammatory polyradiculoneuropathy affects 
people of all ages, but has a peak incidence between 50 
and 70 years of age. In 60% of patients, there is a histo- 
ry of mild respiratory or gastrointestinal infection 1-3 
weeks before onset of neurological symptoms. Sensory 
symptoms predominate with paresthesia, hypoe^thesia, 
weakness and pain in the limb muscles commencing dis- 
tally and ascending to involve the trunk, neck and head. 

CSF analysis shows markedly elevated protein levels. 
Clinical features resolve spontaneously with full recovery 
in most cases although recurrences and a chronic pro- 
gressive course have been described. 

Contrast medium administration is essential to dis- 
close the MRI features of Guillain-Barre syndrome, con- 
sisting of varying degrees of diffuse symmetrical in- 
tradural root enhancement.